Chronic exposure to ozone induces cardiac antioxidant response and overexpression of either mitochondrial fision protein DRP1 and hipertrophyc-related proteins.

Pollution is considered a risk factor for cardiovascular disease; however, the mechanisms to explain this relationship are not well understood; ozone is one of the most abundant and studied air contaminants. Our study aimed to evaluate the effect of chronic exposition of rats to controlled low doses of ozone on oxidative stress, apoptosis, mitochondrial dynamics, and cardiac hypertrophy. Male Wistar rats were daily exposed to low ozone doses during 7, 15, 30, and 60 days, 4 h/day. Hearts were dissected, and homogenates were prepared. Oxidative stress was evaluated by TBARS and protein nitrosylation in addition to Superoxide dismutase 1 (SOD1) and Catalase levels; the apoptosis related-proteins caspase 3, caspase 9, Bax, Bcl-2, and the mitochondrial dynamic-associated proteins Fis1, Drp1, OPA1, and Mfn1 were quantified by western blot among the cardiac hypertrophy indicator alpha-actin (cardiac actin). There were no changes in the oxidative stress markers, however SOD1 expression increases. Caspase 3 expression decreased, whereas caspase 9 increased without changes in Bax or Bcl-2. Mitochondrial fission may be favored according to the increased expression of Drp1 but not changes in fusion-related proteins OPA1 and Mfn1. Finally, the molecular marker for cardiac hypertrophy was overexpressed after 30 and 60 days of ozone exposition. The chronic exposition to ozone induces a deleterious effect on cardiac mitochondria. Antioxidant defenses also show changes in relation to exposure time, as well as an apparent pro-hypertrophic effect associated with altered mitochondrial dynamics.

Oxidative Stress Caused by Ozone Exposure Induces Changes in P2X7 Receptors, Neuroinflammation, and Neurodegeneration in the Rat Hippocampus.

Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-ß (GSK3-ß) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ß) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-ß at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.

Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas.

Pituitary adenomas (PAs) can be unpredictable and aggressive tumors. No reliable markers of their biological behavior have been found. Here, a proteomic analysis was applied to identify proteins in the expression profile between invasive and non-invasive PAs to search for possible biomarkers. A histopathological and immunohistochemical (adenohypophyseal hormones, Ki-67, p53, CD34, VEGF, Flk1 antibodies) analysis was done; a proteomic map was evaluated in 64 out of 128 tumors. There were 107 (84%) invasive and 21 (16%) non-invasive PAs; 80.5% belonged to III and IV grades of the Hardy-Vezina classification. Invasive PAs (n = 56) showed 105 ± 43 spots; 86 ± 32 spots in non-invasive PAs (n = 8) were observed. The 13 most prominent spots were selected and 11 proteins related to neoplastic process in different types of tumors were identified. Hint1 (Histidine triad nucleotide-binding protein 1) high expression in invasive PA was found (11.8 ± 1.4, p = 0.005), especially at high index (>10; p = 0.0002). High Hint1 expression was found in invasive VEGF positive PA (13.8 ± 2.3, p = 0.005) and in Flk1 positive PA (14.04 ± 2.28, p = 0.006). Hint1 is related to human tumorigenesis by its interaction with signaling pathways and transcription factors. It could be related to invasive behavior in PAs. This is the first report on Hint expression in PAs. More analysis is needed to find out the possible role of Hint in these tumors.

An overview of the infection of CMV, HSV 1/2 and EBV in Mexican patients with glioblastoma multiforme.

Several risk factors are involved in glioblastoma, including cytomegalovirus (CMV). This research was carried out to determine the rate of CMV infection, as well as HSV 1/2 and EBV in brain tissue, in patients with glioblastomamultiforme (GBM). The tissues were tested using immunohistochemistry, PCR, in situ hybridization and real-time PCR. At least, one HHV was detected in 21/29 (72%) patients as follows: single infections with HSV-1/2 in 4/21 (19%), EBV in 6/21 (28.6%) and CMV in 1/21 (4.8%). Mixed viral infection, HSV-1/2 and EBV were detected in 4/21 patients (19%), CMV and EBV in 5/21 (23.8%), and HSV-1/2, EBV, and CMV in 1/21. The CMV viral load ranged from 3×102 to 4.33×105 genome/100ng of tissue. Genotype based on CMV gB was 3/7 where 2/3 was gB1 and 1/3 gB4. HSV, EBV and CMV were frequently found in brain tissues, more in mix in a population reported as highly seropositive.

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury.

After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.