Platelet-rich plasma combined with ozone prevents cartilage destruction and improves weight-bearing asymmetry in a surgery-induced osteoarthritis rabbit model.

BACKGROUND: Osteoarthritis (OA) is the most common degenerative disease in older adults and its treatment remains unsatisfactory. This study aimed to evaluate the effectiveness and explore the therapeutic mechanisms of the combination of platelet-rich plasma (PRP) and ozone (O3) for knee OA. METHODS: Thirty male rabbits were randomly divided into five groups (Control group, OA group, PRP group, O3 group, and PRP + O3 group). Rabbit model of OA were induced by improved Hulth surgery. Gross articular observation, histopathological examination and cartilage scoring system were used to assess the articular cartilage destruction. The bone morphogenetic protein-2 (BMP-2) mRNA expression in joint fluid was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of type II collagen, matrix metalloproteinase-1 (MMP-1) of cartilage was detected via Immunohistochemistry. Pain behavior was observed by percent ipsilateral weight-bearing (PIW) asymmetry. RESULTS: The content of platelet in PRP was increased by 6.2-times that in whole blood. Among induced OA groups (the OA, PRP, O3 and PRP + O3 group), PRP + O3 significantly inhibited the surgically induced increase in gross articular alterations, histopathological damage of cartilage and Mankin score when compared to the OA, PRP and O3 groups (P<0.05). Observed pain behavior by weight-bearing asymmetry, in the PRP + O3 group was reversed at 3 and 6 weeks after the administration of PRP + O3 (PIW asymmetry: -10.66%±1.172%). In addition, surgery-induced BMP-2 mRNA expression was significantly downregulated after the treatment of PRP, O3 and PRP + O3 (P<0.01). PRP + O3 group significantly increased the expression of type II collagen but decreased MMP-1 of cartilage in comparison to OA, PRP and O3 groups (P<0.05) by immunohistochemical analysis. CONCLUSIONS: PRP combined with O3 may prevent cartilage destruction and improve weight-bearing asymmetry by restoring homeostasis between anabolism and catabolism of extracellular matrix in progressive OA. Furthermore, a combination of PRP and O3 might achieve even better results than the two agents alone.

Ozone induces BEL7402 cell apoptosis by increasing reactive oxygen species production and activating JNK.

BACKGROUND: Oxidative stress is an important factor in the modulation of both tumorigenesis and anticancer responses. Ozone (O3) is a strong oxidant that causes redox reactions and exerts anticancer effects in various types of cancer cells. However, the pathways involved in O3-induced cell death are not well understood. METHODS: In vitro human hepatocellular carcinoma (HCC) BEL7402 cells were treated with various O3 concentrations to evaluate O3 cytotoxicity by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The regulatory mechanisms were analyzed by western blot analysis. In vivo, an HCC model was established to evaluate the inhibition of HCC with O3 treatment. RESULTS: In vitro cells treated with O3 exhibited a round and small morphology with nuclear shrinkage and fragmentation. The CCK-8 assay confirmed the potent cytotoxic activity of O3 against BEL7402 cells (IC50 value of 5 µg/mL). Acridine orange/ethidium bromide (AO/EB) staining revealed apoptosis of BEL7402 cells after O3 treatment. Flow cytometry analysis showed that S phase cell cycle arrest and apoptosis increased with O3 exposure. In addition, O3 exposure reduced the mitochondrial membrane potential (ΔΨm) and induced reactive oxygen species (ROS) accumulation. Western blot analysis showed that O3 exposure reduced B-cell lymphoma 2 (BCL-2) expression and increased cleaved poly ADP-ribose polymerase (PARP), cytochrome C (Cyt-C), caspase-3, caspase-9, and p-JNK expression. In vivo, treatment with intratumor injection O3 (20 µg/mL) inhibited HCC growth. CONCLUSIONS: Overall, our findings showed that O3 induces BEL7402 cell apoptosis via the intrinsic mitochondria-dependent pathway. Therefore, O3 has therapeutic potential for HCC.

PM2.5, NO2, wildfires, and other environmental exposures are linked to higher Covid 19 incidence, severity, and death rates.

Numerous studies have linked outdoor levels of PM2.5, PM10, NO2, O3, SO2, and other air pollutants to significantly higher rates of Covid 19 morbidity and mortality, although the rate in which specific concentrations of pollutants increase Covid 19 morbidity and mortality varies widely by specific country and study. As little as a 1-µg/m3 increase in outdoor PM2.5 is estimated to increase rates of Covid 19 by as much as 0.22 to 8%. Two California studies have strongly linked heavy wildfire burning periods with significantly higher outdoor levels of PM2.5 and CO as well as significantly higher rates of Covid 19 cases and deaths. Active smoking has also been strongly linked significantly increased risk of Covid 19 severity and death. Other exposures possibly related to greater risk of Covid 19 morbidity and mortality include incense, pesticides, heavy metals, dust/sand, toxic waste sites, and volcanic emissions. The exact mechanisms in which air pollutants increase Covid 19 infections are not fully understood, but are probably related to pollutant-related oxidation and inflammation of the lungs and other tissues and to the pollutant-driven alternation of the angiotensin-converting enzyme 2 in respiratory and other cells.

Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders.

Systems medicine is founded on a mechanism-based approach and identifies in this way specific therapeutic targets. This approach has been applied for the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Nrf2 plays a central role in different pathologies including neurodegenerative disorders (NDs), which are characterized by common pathogenetic features. We here present wide scientific background indicating how a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagy properties such as the ozone (O3) can represent a potential new strategy to delay neurodegeneration. Our hypothesis is based on different evidence demonstrating the interaction between O3 and Nrf2 system. Through a meta-analytic approach, we found a significant modulation of O3 on endogenous antioxidant-Nrf2 (p < 0.00001, Odd Ratio (OR) = 1.71 95%CI:1.17-2.25) and vitagene-Nrf2 systems (p < 0.00001, OR = 1.80 95%CI:1.05-2.55). O3 activates also immune, anti-inflammatory signalling, proteasome, releases growth factors, improves blood circulation, and has antimicrobial activity, with potential effects on gut microbiota. Thus, we provide a consistent rationale to implement future clinical studies to apply the oxygen-ozone (O2-O3) therapy in an early phase of aging decline, when it is still possible to intervene before to potentially develop a more severe neurodegenerative pathology. We suggest that O3 along with other antioxidants (polyphenols, mushrooms) implicated in the same Nrf2-mechanisms, can show neurogenic potential, providing evidence as new preventive strategies in aging and in NDs.

Investigating associations between anti-nuclear antibody positivity and combined long-term exposures to NO2, O3, and PM2.5 using a Bayesian kernel machine regression approach.

BACKGROUND: Air pollution has many adverse health effects, but the combined or synergistic effects of multiple ambient air pollutants on anti-nuclear antibodies (ANA, a serologic marker of systemic autoimmune rheumatic disease, SARDs) have never been assessed. OBJECTIVE: To flexibly model ANA and individual and joint associations of long-term exposures to nitrogen dioxide (NO2), ozone (O3), and fine particles matter (PM2.5) using a Bayesian Kernel machine regression (BKMR) approach and to compare the results to those from individual logistic regressions. METHODS: Serum ANA positivity was determined for randomly selected CARTaGENE general population subjects in Quebec, Canada. CARTaGENE is a public research platform created for investigating the associations of environmental, genomic, and lifestyle factors on chronic diseases. Ambient NO2, O3, and PM2.5 estimates, derived from ground-measurement and chemical-transport-model simulated concentrations, were assigned to subjects based on residential postal codes at the time of blood collection. Our models adjusted for age, sex, French Canadian origin, smoking, and family income. RESULTS: Concentrations of NO2, O3, and PM2.5 were closely correlated in space. In the 5485 CARTaGENE subjects studied, we did not see clear associations between NO2, PM2.5 or O3 and ANA positivity, with either the BKMR or logistic models. CONCLUSIONS: BKMR did not uncover associations between ANA positivity and individual levels or combined exposures of NO2, O3, and PM2.5; neither did simpler logistic models. Additional studies (in younger populations, in distinct race/ethnicity groups, and/or in jurisdictions with high air pollution levels) would be helpful to reinforce current findings.

Gas exchange and chlorophyll fluorescence of pea (Pisum sativum L.) plants in response to ambient ozone at a rural site in Egypt.

Egyptian pea cultivars (Pisum sativum L. cultivars Little Marvel, Perfection and Victory) grown in open-top chambers were exposed to either charcoal-filtered (FA) or non-filtered air (NF) for five consecutive years (2009-2013) at a rural site in northern Egypt. Net photosynthetic rates (PN), stomatal conductance (gs), intercellular CO2 (Ci) and chlorophyll fluorescence were measured. Ozone (O3) was found to be the most prevalent pollutant common at the rural site and is suspected to be involved in the alteration of the physiological parameters measured in the present investigation. PN of different cultivars were found to respond similarly; decreases of 23, 29 and 39% were observed in the cultivars Perfection, Little Marvel and Victory, respectively (averaged over the five years) due to ambient O3. The maximum impairment in PN was recorded in the cultivar Victory (46%) in 2013 when the highest O3 levels were recorded (90 nL L(-1)). The average stomatal conductance decreased by 20 and 18% in the cultivars Little Marvel and Perfection, respectively, while the average stomatal conductance increased on average by 27% in the cultivar Victory. A significant correlation was found between PN and Ci, indicating the importance of non-stomatal limitations of photosynthesis, especially in the cultivar Victory. The PN vs. Ci curves were fitted to a non-rectangular hyperbolic model. The actual quantum yield (ΦPSII) and photochemical quenching coefficient (qP) were significantly decreased in the leaves of plants exposed to NF air. Non-photochemical quenching (NPQ) was increased in all cultivars. Exposure to NF air caused reductions in chlorophyll (Chl a) of 19, 16 and 30% in the Little Marvel, Perfection and Victory cultivars, respectively.

Ozone-induced ethylene and foliar injury responses are altered in 1-aminocyclopropane-1-carboxylate synthase antisense potato plants.

• In potato (Solanum tuberosum), two 1-aminocyclopropane-1-carboxylate synthase (ACS) genes are induced by ozone (O3 ). Antisense inhibition of these ethylene (C2 H4 ) biosynthetic genes allowed us to examine the relationship between O3 -induced C2 H4 emission and foliar injury. • Thirty-two lines (antisense for ST-ACS4 or ST-ACS5) were screened in the glasshouse for acute O3 -induced C2 H4 and lesions. Stomatal conductance and ACS transcripts were quantified for selected C2 H4 -altered lines. Six lines were field-tested for chronic O3 effects. • Ten lines produced less, and four lines produced more, acute-O3 -induced C2 H4 than nontransformed (NT) plants. Ethylene levels did not appear to be correlated with stomatal conductance. ST-ACS4 and -5 transcript were reduced in transgenic plants, except in two C2 H4 over-producing lines. In the field, these C2 H4 over-producing lines displayed stunting and leaf rolling in charcoal-filtered (CF) air and chronic O3 , and they sustained the most severe O3 injury. • When C2 H4 production was strongly suppressed or enhanced, corresponding reductions or increases in lesion severity were observed, suggesting a critical role for C2 H4 in the lesion formation process during O3 stress.