Search Results (162)

Background: Oxygen–ozone (O₂–O₃) therapy is a minimally invasive treatment for discogenic lumbar pain. Although rare, spinal infections—specifically spondylodiscitis—have been reported following intradiscal injections. To date, Lactobacillus iners has not been described as a causative agent in this context. Case Presentation: A 55-year-old immunocompetent woman presented with progressive lumbosciatica and elevated inflammatory markers three months after intradiscal O₂–O₃ therapy. MRI revealed L4–L5 spondylodiscitis with paravertebral involvement. Surgical biopsy confirmed L. iners as the pathogen. She underwent decompression and received targeted intravenous antibiotics, achieving full clinical and radiological recovery. Methods: A systematic literature review was performed using PubMed, MEDLINE, and Scopus to identify reports of spondylodiscitis following oxygen–ozone therapy. Six cases were included based on predefined inclusion criteria. Results: The 8 identified cases involved a range of pathogens, including Staphylococcus aureus, Streptococcus beta-haemolyticus, Escherichia coli, Achromobacter xylosoxidans, Mycobacterium abscessus, and Streptococcus intermedius, and one culture-negative infection. Clinical presentations varied from radiculopathy to sepsis. Management strategies encompassed both conservative (antibiotics alone) and surgical approaches, depending on neurological status and abscess formation. Outcomes were favorable in all cases except one fatality. Conclusions: This report is the first to describe L. iners spondylodiscitis in an immunocompetent patient following O₂–O₃ therapy. Clinicians should vigilantly evaluate post-infiltration spinal infections, maintain a low threshold for imaging and biopsy, and implement pathogen-targeted antibiotic regimens, with surgical intervention as needed. Full article

Background: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) represents an emerging challenge in veterinary dermatology. Commercially available ozonated oils promise antibacterial activity, but their efficacy under physiologically relevant conditions remains unexplored. Objective: We aimed to evaluate the efficacy of commercial ozonated olive oil product (800 mEq O₂/kg) against MRSP using an established in vitro model and a newly presented ex vivo canine skin model. Materials and Methods: In vitro susceptibility testing determined minimum inhibitory concentrations (MIC) and time–kill kinetics. Subsequently, canine skin samples were mounted in Franz diffusion cells, inoculated with MRSP (~10⁶ colony-forming units [CFU]), and treated for 8 h with ozonated or placebo olive oil. Bacterial viability was assessed by quantitative culture and histopathology. Results: In vitro testing demonstrated antibacterial activity for ozonated oil (MIC < 20% v/v) compared to placebo oil (90% v/v), with ozonation-specific bactericidal effects. However, ex vivo testing showed no MRSP reduction for either oil versus untreated controls, with bacterial localization in superficial dermis unchanged. Conclusions: Despite in vitro activity, this ozonated olive oil failed to reduce MRSP in ex vivo skin, revealing that tissue barriers prevent antibacterial delivery. These findings demonstrate that in vitro screening cannot predict topical efficacy and emphasize the necessity of tissue-based validation before clinical use. Full article

In the last decades, ozone (O₃)-based medical treatments have become a widely applied complementary therapy for several pathological conditions. O₃ is administered at low dosages since the induction of a mild oxidative stress does not cause damage but stimulates the antioxidant cell response through the nuclear factor erythroid 2-related factor 2 (Nrf2). Mitochondria are sensitive to even mild oxidative stress, thus being a responsive target for O₃. This study aimed to evaluate the mitochondrial response to low O₃ doses used for medical treatments. As the skeletal muscle represents a primary target in local O₃ treatments, a murine non-tumoral muscle cell line was selected as an appropriate in vitro model. Transmission electron microscopy, biochemistry, and flow cytometry provided original information on the O₃ dose-dependent modifications of mitochondrial structural and molecular features. Low O₃ doses promoted an increase in mitochondrial area and in cristae extension, as well as an enhancement of the electron transport chain complexes and of antioxidant catalase and manganese-dependent superoxide dismutase. Nrf2 maintained its association with the outer mitochondrial membrane, thus exerting its protective role. All mitochondrial modifications were observed 24 h after treatment and disappeared after 48 h, demonstrating that cells promptly respond to the O₃-driven oxidative stress, effectively restoring homeostasis. Full article

Background: The solid Ehrlich tumor (SET) is a transplantable experimental neoplasm that mimics mammary adenocarcinoma in female mice, widely used to investigate tumor physiology, behavior, and therapeutic interventions. Among emerging approaches, ozone therapy has gained attention in human and veterinary medicine, prompting studies to clarify its mechanisms and potential applications. This study evaluated vascular and tumor cell proliferation in SET of mice treated with ozonated water under different protocols. Methods: A total of 99 animals were allocated into four groups: ozonated water at 104 mM/5 ppm (G1, n = 30), 208 mM/8 ppm (G2, n = 30), vehicle control with 0.9% saline (G3, n = 30), and negative control (GCN, n = 9). Subgroups were established according to administration routes (intratumoral or peritumoral), number of applications (one or two), and observation periods (24 h, five days, or 30 days). Immunohistochemistry with anti-CD31 and anti-Ki-67 antibodies assessed vascular and cellular proliferation, respectively, considering peri- and intratumoral regions. Results: Increased CD31 expression was detected at 30 days in treated groups compared to controls, particularly after two intratumoral applications and in all peritumoral (PT) protocols. Ki-67 expression was reduced after five days in the treated groups, indicating decreased cell proliferation relative to controls. A positive correlation was observed between peri- and intratumoral CD31 immunostaining. Conclusion: Ozonated water reduced tumor cell proliferation in the medium term, but treatment discontinuation favored increased vascular density in the long term. These findings suggest caution in the oncological use of ozone, as it may present both antineoplastic and tumor-promoting effects depending on treatment conditions. Full article

Background/Objectives: Mild cognitive impairment (MCI) is accompanied by olfactory dysfunction, and few interventions target shared chemosensory–cognitive mechanisms. We retrospectively examined whether a 5-week oxygen–ozone major autohemotherapy (MAH) cycle is associated with coupled improvements in olfactory and cognitive performance in adults with MCI. Methods: We analyzed 81 individuals with MCI who completed 10 MAH sessions (twice weekly) and 93 matched healthy controls. In the MCI group, olfactory function was measured before and after MAH using Sniffin’ Sticks^® threshold–discrimination–identification (TDI) scores; global cognition was assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). We evaluated between-group and pre–post changes and used Spearman correlations to assess olfactory–cognitive coupling. Results: At baseline, MCI participants showed lower TDI and MoCA scores than controls and more hyposmia/anosmia. Following MAH, the proportion of normosmic patients increased from 32.1% to 50.6%, with fewer anosmic cases. TDI scores improved but remained lower than in controls. MMSE scores were unchanged, whereas MoCA total scores increased, with domain-level gains and a significant improvement in Language Repetition. TDI gains were modestly correlated with MoCA total and selected domain changes. Conclusions: In this retrospective cohort, MAH was associated with partial restoration improvements of olfactory function and improved cognitive performance. Correlated olfactory–cognitive changes were observed within the treated MCI group; however, causal attribution to O₂–O₃ MAH cannot be established without randomized, double-blind, sham-controlled trials with coupled olfactory–cognitive gains consistent with a shared, potentially modifiable substrate. Prospective randomized trials are needed to confirm efficacy and clinical utility. Full article

Objectives: To evaluate the clinical effectiveness and safety of natural products compared with chlorhexidine (CHX) as adjuncts to non-surgical periodontal therapy (NSPT) in patients with periodontitis. Materials and Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (CRD420251133219). Electronic searches of PubMed, Scopus, and Web of Science were performed to identify randomized controlled trials (RCTs) published between 2020 and 2025. Eligible studies included adult patients with periodontitis treated with NSPT, comparing CHX-based products with natural formulations (mouthwashes, gels, irrigants, or dentifrices). Data extraction included product type, concentration, mode of application, follow-up duration, and primary periodontal outcomes. Study quality was assessed using the NIH Quality Assessment Tool. Results: Thirteen randomized controlled clinical trials met the inclusion criteria. Natural products such as Curcuma longa, Morus alba, Spirulina platensis, Propolis, Triphala, and Lycium barbarum demonstrated improvements in clinical attachment level (CAL) and probing pocket depth (PPD) comparable to those obtained with CHX, along with significant reductions in bleeding on probing (BoP) and plaque index (PI). Probiotic- and ozone-based treatments also showed favorable clinical outcomes, with faster healing and fewer adverse effects, such as tooth staining and taste alteration. Follow-up periods ranged from 14 days to 3 months. Conclusions: Natural products appear to be safe and effective alternatives to CHX when used as adjuncts to non-surgical periodontal therapy, providing comparable clinical benefits with a lower incidence of side effects. Nevertheless, further large-scale, long-term randomized trials are needed to standardize formulations and concentrations and to confirm the durability of these clinical effects. Full article

Background: Periodontal disease results from a complex interaction between the microbial biofilm and the host immune response. The aim of this study was to evaluate and compare, in samples of dental plaque in periodontal patients, the presence of periodontal bacteria before and after two different non-surgical treatments: ozone (O₃) therapy and a desiccant agent (HybenX, HBX, administered one or three times). Methods: Molecular biology techniques were used to estimate the effect of the two treatments on different periodontal pathogen microorganisms. The presence of Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Tannerella forsythia, Actinomyces naeslundii and Aggregatibacter actinomycetemcomitans was investigated by multiplex PCR (mPCR) and quantitative PCR (qPCR) at baseline (T = 0, before oral hygiene), one week (T = 1), two weeks (T = 2), one month (T = 3) and three months (T = 4) after treatment. Results: P. intermedia was the most frequently detected pathogen in the study population, further quantified by qPCR in samples positive to mPCR at baseline (T = 0) and at the end of treatment (T = 4). The qPCR results showed evident decreases in load after treatment with HBX ^x1, HBX ^x3 and O₃; nevertheless, comparison between groups and between time points (from T = 0 to T = 4) did not show any significant differences (p = 0.3 and p = 0.8). For P. gingivalis, the O₃ therapy showed a reduction in detection after two weeks and after one month, while HBX showed a great reduction in its presence when administered three times. Conclusion: Both agents were effective in reducing the presence of the periodontal pathogens in the dental pockets of patients affected by chronic periodontal diseases. In particular, HBX applied three times showed greater improvement compared to a single application. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Background and Clinical Significance: Breast cancer is the most frequent malignancy in women. Metastatic breast cancer is considered a treatable but incurable condition, with a median overall survival of only 2–3 years. Among its subtypes, triple-negative breast cancer (TNBC) accounts for a high proportion of breast cancer-related deaths. It is characterized by an aggressive clinical course, early recurrence, and a strong propensity for visceral and brain metastases. Case Presentation: We report the case of a Caucasian woman who developed systemic disease recurrence with lung and mediastinal lymph node metastases, occurring two years after her primary diagnosis and treatment for TNBC. The patient received three months of chemotherapy combined with an adjuvant integrative protocol consisting of melatonin, cannabidiol, and oxygen–ozone therapy. This combined approach led to the complete disappearance of the lung nodules. Subsequently, stereotactic radiotherapy was performed and, in association with the ongoing integrative treatment, resulted in a significant reduction in mediastinal adenopathy. Introduction of immunotherapy, supported continuously by the same adjuvant strategy, achieved a complete and durable remission. Strikingly, the patient remained disease-free five years after the diagnosis of lung and mediastinal metastases. Conclusions: This clinical case highlights the potential benefit of using melatonin, cannabidiol, and oxygen–ozone therapy as part of an integrative approach in patients with aggressive metastatic TNBC. While it is not possible to establish causality from a single case, the sustained remission observed suggests that such unconventional adjuvant strategies could play a supportive role in enhancing the efficacy of standard oncologic therapies. Full article

Background: This retrospective study evaluated the association between the number of intra-articular ozone injection sessions and clinical outcomes in patients with hip osteoarthritis (OA). Methods: Data from 54 patients (65 hips) with Tönnis grade 1–2 hip OA treated at a tertiary algology clinic between 2022 and 2024 were analyzed. Patients were categorized into three groups based on the number of ozone sessions received (1, 2, or 3). Pain and functional status were assessed using the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index at baseline and at 4, 12, and 24 weeks post-procedure.Results: All groups demonstrated significant improvements in VAS and WOMAC scores compared to baseline (p < 0.001). Although the three-session group showed more pronounced numerical improvements in both early and late follow-ups, intergroup differences did not consistently reach statistical significance across all time points.Conclusions: Intra-articular ozone application is associated with favorable clinical trends in pain reduction and functional recovery. Our findings suggest that a three-session regimen may provide more pronounced clinical improvement compared to fewer sessions. These findings warrant validation through rigorous, randomized controlled trials. Full article

Background: Autologous platelet concentrates, including platelet-rich fibrin (PRF) matrices, have been proposed as biologically active scaffolds for vital pulp therapy. Evidence on the clinical use of different solid PRF matrices for direct pulp capping remains limited. Objective: The aim of this study is to describe and monitor two clinical cases of reversible pulpitis treated with direct pulp capping using two PRF membranes prepared by different centrifugation approaches, namely advanced platelet-rich fibrin plus (A-PRF+) and horizontal platelet-rich fibrin plus (H-PRF). Methods: In Case 1, A-PRF+ was prepared using a fixed-angle centrifugation protocol; in Case 2, H-PRF was prepared using a horizontal centrifugation protocol. In both cases, deep carious lesions with small carious pulp exposures (<1.5 mm) were managed by caries removal, ozone-assisted dentin disinfection, and direct pulp capping with the respective PRF membrane, followed by temporary calcium-silicate cement definitive coronal restoration. Clinical and radiographic follow-up, including cone-beam computed tomography, was performed for up to 12 months. Results: In Case 1 (A-PRF+), reparative dentin bridge formation was confirmed at 90 days, with a thickness of 0.2 mm. In Case 2 (H-PRF), reparative dentin was observed within 46 days, with a thickness of 0.28 mm. In both cases, pulp vitality was maintained, and no clinical symptoms or periapical changes were detected during the 12-month follow-up. Conclusions: These two cases suggest that direct pulp capping using PRF membranes (A-PRF+ or H-PRF), combined with ozone-assisted dentin disinfection and adequate coronal sealing, may be associated with maintained pulp vitality and hard-tissue repair after carious pulp exposure diagnosed as reversible pulpitis. Due to the descriptive two-case design and major confounding factors (including age and lesion characteristics), no comparative conclusions can be drawn. Prospective controlled clinical studies with standardized protocols are warranted. Full article

Background/Objectives: Psoriasis is a chronic, inflammatory, systemic skin disease. Although topical and systemic drugs with proven effectiveness are used in the treatment, ozone therapy is also applied as a treatment option based on clinical personal experience and with limited published knowledge. In this project, the aim was to evaluate the effectiveness of major ozone therapy in psoriasis patients together with biomarkers in serum. Methods: A total of 26 psoriasis patients and 19 healthy controls were included in the study. The disease severity was evaluated by the psoriasis area severity index score and grouped as mild, moderate/severe. Serum tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), high-sensitivity C-reactive protein (Hs-CRP), sialic acid, and Sialic acid binding Ig-like Lectin-14 (Siglec-14) levels were investigated in controls and psoriasis patients. Results: Psoriasis area severity index (PASI) score decreased significantly in psoriasis patients after ozone autohemotherapy application (p < 0.005). The values of IL-1β, sialic acid, and Siglec-14 after treatment in healthy subjects were statistically significantly higher than in psoriasis patients. It was found that Hs-CRP and Siglec-14 decreased in all patients after treatment, Hs-CRP decreased more significantly in mild psoriasis patients, and Siglec-14 decreased in both mild and moderate-severe groups (p < 0.05). Conclusions: Our research results suggest that ozone autohemotherapy has clinical efficacy in psoriasis patients, inflammation also has a role in the mechanism of action, and its effectiveness in treatment can be evaluated with inflammation markers. Full article

Limb wounds in horses represent a significant therapeutic challenge due to poor vascularization, reduced skin elasticity, and high risk of complications such as exuberant granulation tissue. Conventional treatments sometimes fail to provide satisfactory healing outcomes, leading to prolonged recovery and increased costs. This study aimed to evaluate the efficacy of topical ozone therapy using the bagging method in promoting the epithelialization and contraction of chronic distal limb wounds in horses refractory to conventional management. Eight horses, aged 3–21 years, with chronic wounds averaging 48.79 ± 21.20 cm², were treated exclusively with ozone (50 μg/mL) administered by bagging for 30 min every 48 h until complete healing. All cases achieved full wound closure within 27–91 days without systemic medication or major complications. Macroscopic evaluation showed favorable healing, with the restoration of skin pigmentation and hair growth in most cases, while only minimal fibrous scarring was observed in a few patients. Statistical analysis revealed significant improvements in epithelialization, particularly during the last four weeks of treatment. These findings suggest that ozone bagging therapy is a simple, cost-effective, and well-tolerated method that may enhance the healing of chronic distal limb wounds in horses. Further controlled trials are needed to standardize treatment protocols and compare ozone with conventional therapies. Full article

Background/Aim: This systematic review and meta-analysis aimed to evaluate the clinical efficacy of oxygen-based adjunct therapies in patients with periodontitis, including ozone therapy, hyperbaric oxygen therapy, and local oxygen delivery, as adjuncts to subgingival instrumentation. These interventions have been proposed to counteract tissue hypoxia and inflammation, which sustain an environment favorable to anaerobic pathogens in periodontitis. Methods: An electronic search was conducted in MEDLINE PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials, and SciELO. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Standardized mean difference was calculated for gains in clinical attachment level, and a random effects model was applied due to high variability. Results: The meta-analysis of adjunct ozone therapies presented a pooled standardized mean difference of 0.53 (95% CI [−0.14, 1.19]), indicating a clinically relevant medium effect in favor of ozone therapies, though this effect was not statistically significant and substantial heterogeneity was observed (I² = 70%, p < 0.01). Meta-analysis was restricted to adjunct ozone therapies due to the limited availability of qualifying studies for hyperbaric oxygen therapy and local oxygen therapies. Conclusions: While the medium effect size in favor of ozone therapies could be clinically relevant, the statistical non-significance underscores the need for more evidence before widespread adoption. Individual studies reported significant benefits for adjunct HBOT and ozonated olive oil, but comparison between oxygen delivery modes was not possible due to heterogeneous protocols. Full article

Research Subject: Primary and secondary immunodeficiencies represent a growing clinical and public health challenge due to increased susceptibility to infections, impaired immune regulation, chronic inflammation, and disturbances in redox homeostasis. The pathophysiology of these disorders involves dysfunction of innate and adaptive immunity, altered cytokine production, oxidative stress, and reduced activity of antioxidant defense mechanisms. In recent years, attention has increasingly focused on the role of oxidative imbalance and chronic inflammation in weakening immune function. Ozone therapy, when used at controlled low doses, induces a hormetic response that triggers adaptive antioxidant pathways, modulates cytokine profiles, and enhances the activity of immune cells. Due to these properties, ozone has emerged as a potential adjunctive therapy aimed at restoring immune homeostasis and improving clinical outcomes in patients with immune disorders. Aim of Study: The aim of this review is to discuss the role of oxidative stress and immune dysregulation in the pathogenesis of immunodeficiencies and to provide an updated overview of current evidence regarding the therapeutic potential of ozone therapy. This article summarizes molecular mechanisms, biochemical effects, and clinical findings related to ozone-based interventions, with particular emphasis on cytokine modulation, redox balance, macrophage function, regulatory T cells (Treg), and NK cell activity. Materials and Methods: This review is based on scientific data retrieved from PubMed, Scopus, and Google Scholar. Included sources comprise randomized clinical trials, observational studies, meta-analyses, mechanistic studies, and review articles published between 1996 and 2025. Keywords used during the literature search included: “ozone therapy”, “immunomodulation”, “oxidative stress”, “inborn errors of immunity”, “secondary immunodeficiency”, “Treg cells”, “redox homeostasis”. Results: Analysis of current studies shows that controlled low-dose ozone (typically 10–40 µg/mL) activates the Nrf2/ARE antioxidant pathway, increases enzymatic defense (SOD, catalase, GPx), and reduces levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Clinical trials report improved lymphocyte profiles, enhanced macrophage phagocytic function, increased Treg activity, and reinforced NK cell responses. Patients receiving ozone therapy demonstrate reductions in inflammatory markers (CRP, IL-6, D-dimer), improved redox balance, decreased infection frequency, and better overall immune performance. The therapy is generally well tolerated when administered within established safety guidelines. Conclusions: Available evidence indicates that ozone therapy may serve as a valuable adjunct in the management of immunodeficiencies by modulating immune responses, reducing oxidative stress, and restoring homeostatic balance. Although current clinical outcomes are promising, further multicenter randomized trials are needed to standardize dosing protocols, assess long-term effectiveness, and confirm safety. Full article