Impact of ozone therapy on mouse liver mitochondrial function and antioxidant system.

Ozone therapy's efficacy might stem from the regulated and mild oxidative stress resulting from ozone's interactions with various biological elements. The present work aimed to characterize the hepatic mitochondrial response to ozone treatment and its relationship with the antioxidant system response. Two groups of mice were used: one control group and another injected intraperitoneally with an O3/O2 mixture (80 ml/kg) for 5 days. Mitochondrial respiration supported by different substrates was significantly inhibited, as well as complexes I and II/III, but not complex IV. The analysis of the electron transport chain complex activity showed significant inhibitions in complexes I and II/III but not in complex IV. These inhibitions can prevent mitochondrial reactive oxygen species (ROS) production. Additionally, there was a decline in glutathione content, unaccompanied by a rise in its oxidized form. The ozone-treated groups showed a significant increase in the activity of superoxide dismutase and glutathione peroxidase, while catalase and glutathione reductase experienced no significant alterations. Adenine nucleotides increased in the ozone group, but only the increase in adenosine diphosphate is significant, so the cell's energy charge is unaffected. This study shows that mitochondria may play a crucial role in ozone treatment. However, it also highlights the need for further studies to understand the molecular mechanism.

Physical Inactivity is Liable to the Increased Cardiovascular Risk and Impaired Cognitive Profile.

BACKGROUND: Sedentary life-style is a significant public health issue. It increases the incidence of type-2 diabetes mellitus (DM2) and systemic arterial hypertension (SAH), which in turn may impair physical and mental health. In fact, disrupted glucose metabolism is characteristic of Alzheimer's dementia, and it is often dubbed as type-3 diabetes. OBJECTIVE: The purpose of this study was to assess the level of activity, body composition, cardiovascular risk and cognitive profile of patients with DM2 and/or SAH. The study was cross-sectional design. METHOD: The sample consisted of 120 individuals which 35% men and 65% women, with an average of 64±9 years old and 60±11 years old, respectively. Various parameters were evaluated such as anthropometric variables, pedometer recordings and brief cognitive screening battery (BCSB), which assesses the immediate memory, verbal fluency, learning, late memory and recognition. Chi-square and Fisher's exact test were applied to observe possible differences between men and women. In addition to Kruskall-Wallis, in the comparison between patients with SAH; DM2 and SAH + DM2. RESULTS: A high rate of physical inactivity was found among those enrolled in this project. Females were characterized by increased body fat, whereas men displayed visceral fat excess. BCSB demonstrated reduced verbal fluency, late memory and recognition, with women presenting significantly worse results. CONCLUSION: Low level of daily physical activity is apparently correlated with obesity, elevated cardiovascular risk, and cognitive dysfunction.

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism's biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

Melanopsin and rhodopsin mediate UVA-induced immediate pigment darkening: Unravelling the photosensitive system of the skin.

The mammalian skin has a photosensitive system comprised by several opsins, including rhodopsin (OPN2) and melanopsin (OPN4). Recently, our group showed that UVA (4.4 kJ/m2) leads to immediate pigment darkening (IPD) in murine normal and malignant melanocytes. We show the role of OPN2 and OPN4 as UVA sensors: UVA-induced IPD was fully abolished when OPN4 was pharmacologically inhibited by AA9253 or when OPN2 and OPN4 were knocked down by siRNA in both cell lines. Our data, however, demonstrate that phospholipase C/protein kinase C pathway, a classical OPN4 pathway, is not involved in UVA-induced IPD in either cell line. Nonetheless, in both cell types we have shown that: a) intracellular calcium signal is necessary for UVA-induced IPD; b) the involvement of CaMK II, whose inhibition, abolished the UVA-induced IPD; c) the role of CAMK II/NOS/sGC/cGMP pathway in the process since inhibition of either NOS or sGC abolished the UVA-induced IPD. Taken altogether, we show that OPN2 and OPN4 participate in IPD induced by UVA in murine normal and malignant melanocytes through a conserved common pathway. Interestingly, upon knockdown of OPN2 or OPN4, the UVA-driven IPD is completely lost, which suggests that both opsins are required and cooperatively signal in murine both cell lines. The participation of OPN2 and OPN4 system in UVA radiation-induced response, if proven to take place in human skin, may represent an interesting pharmacological target for the treatment of depigmentary disorders and skin-related cancer.

Melanopsin, a Canonical Light Receptor, Mediates Thermal Activation of Clock Genes.

Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects of heat shock on the localization of melanopsin by immunocytochemistry. In both cell lines melanopsin was found in a region capping the nucleus and heat shock did not affect its location. The heat-induced increase of Per1 expression was inhibited when melanopsin was pharmacologically blocked by AA92593 as well as when its protein expression was suppressed by siRNA in both Melan-a and B16-F10 cells. These data strongly suggest that melanopsin is required for thermo-reception, acting as a thermo-opsin that ultimately feeds the local circadian clock in mouse melanocytes and melanoma cells.

Dexamethasone Modulates Nonvisual Opsins, Glucocorticoid Receptor, and Clock Genes in Danio rerio ZEM-2S Cells.

Here we report, for the first time, the differential cellular distribution of two melanopsins (Opn4m1 and Opn4m2) and the effects of GR agonist, dexamethasone, on the expression of these opsins and clock genes, in the photosensitive D. rerio ZEM-2S embryonic cells. Immunopositive labeling for Opn4m1 was detected in the cell membrane whereas Opn4m2 labeling shows nuclear localization, which did not change in response to light. opn4m1, opn4m2, gr, per1b, and cry1b presented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression of per1b and cry1b transcripts to ZT16, which corresponds to the highest opn4m1 expression. Interestingly, DEX promoted an increase of per1b expression when applied in LD condition but a decrease when the cells were kept under DD condition. Although DEX effects are divergent with different light conditions, the response resulted in clock synchronization in all cases. Taken together, these data demonstrate that D. rerio ZEM-2S cells possess a photosensitive system due to melanopsin expression which results in an oscillatory profile of clock genes in response to LD cycle. Moreover, we provide evidence that glucocorticoid acts as a circadian regulator of D. rerio peripheral clocks.

Estilo de vida de acadêmicos de educação física de uma universidade pública do estado de Sergipe, Brasil / Lifestyle among physical education students of a public university in Sergipe, Brazil / Estilo de vida de los estudiantes de educación física de una universidad pública en Sergipe, Brasil

Objetivou-se analisar o estilo de vida de acadêmicos de Educação Física de uma universidade pública do estado de Sergipe, Brasil. A amostra probabilística foi de 217 alunos da Universidade Federal de Sergipe com 20,6 (±3,1) anos de idade, sendo 105 da licenciatura e 112 do bacharelado. Da amostra analisada, 3,3% (IC95%: 0,9-1,6) apresentou um estilo de vida inadequado. A maior parte dos alunos, 57,4% (IC95%: 50,7-64,0), não atendeu as recomendações para atividade física. Estudantes da licenciatura estavam mais inadequados que os do bacharelado no conjunto do estilo de vida global e nas condutas de sono, cinto de segurança, estresse e sexo seguro. Os achados contribuem para que a universidade elabore campanhas e programas de extensão no campus para promoção do estilo de vida saudável.

The objective was to analyze the lifestyle in Physical Education students at a public university in Sergipe, Brazil. The random sample was 217 students at Federal University of Sergipe, 20.6 (± 3.1) years old, with 105 of the graduate and 112 of the bachelor. The prevalence of inappropriate lifestyle was 3.3% (95%CI: 0.9-1.6) among the students studied. Most students, 57.4% (95%CI: 50.7 -64.0), didn't meet recommendations for physical activity. The graduate students were more inadequate than bachelor's students in the global lifestyle and in the sleep, safety belt, stress and safe sex behaviors. The findings contribute to the university to develop campaigns and outreach programs on campus to promote healthier lifestyle.

Se tuvo como objetivo analizar el estilo de vida de los estudiantes de Educación Física en una universidad pública en Sergipe, Brasil. La muestra aleatoria de 217 estudiantes de la Universidad Federal de Sergipe con 20.6 (± 3.1) años de edad, siendo 105 estudiantes de graduación e 112 de bachillerato. El estudio demonstró que 3.3% (IC 95%: 0,9 - 1,6) tenía un estilo de vida inadecuado. La mayoría de los estudiantes, 57,4% (IC 95%: 50,7 - 64,0), no cumplir con las recomendaciones de actividad física. Los estudiantes de graduación fueron más inadecuados que el bachillerato en todo el estilo de vida global y en el comportamiento del sueño, estrés, cinturón de seguridad y sexo seguro. Los resultados contribuyen a la universidad para desarrollar campañas y programas de extensión en el campus para promover el saludable estilo de vida.

Estágios de mudança de comportamento para atividade física e fatores associados em acadêmicos de educação física / Stages of behavior change for physical activity and associated factors in physical education students

Este trabalho teve o intuito de identificar e verificar a associação entre os Estágios de Mudança de Comportamento (EMC) para atividade física (AF) com fatores sociodemográficos e comportamentos relacionados à saúde em acadêmicos de Educação Física. A amostra foi calculada considerando o curso, licenciatura e bacharelado, sendo composta por 217 estudantes (54,8% do sexo masculino). Para a avaliação do EMC foi utilizado o questionário de Marcus et al. O comportamento para AF foi dicotomizado em ativo e inativo. As variáveis sociodemográficas analisadas foram: sexo, idade, nível econômico, estado civil, trabalho remunerado, escolaridade da mãe e curso. Os comportamentos relacionados à saúde foram analisados pela auto-percepção de saúde e alimentação. A regressão de Poisson foi usada para examinar as associações entre os EMC para AF com os aspectos sociodemográficos e comportamentos de saúde, considerando p=0,05. A maior parte dos estudantes encontrava-se no estágio de manutenção (38,7%). A prevalência de universitários com comportamento inativo (estágios de pré-contemplação, contemplação e preparação) foi de 45,2%. Os resultados na análise ajustada indicaram que universitários do sexo feminino (RP: 1,64; IC95%: 1,21-2,23) apresentaram maiores probabilidades de terem um comportamento inativo em comparação ao masculino. Escolaridade materna menor do que nove anos foi um fator de proteçãopara apresentar um comportamento inativo (RP: 0,66; IC95%: 0,45-0,99). Tais achados podem ser úteis para o desenvolvimento de programas de promoção da saúde na universidade, com atenção especial aos alunos do sexo feminino e com escolaridade materna elevada.

The objective was to identify and verify the association between the Stages of Behavior Change (SBC) for physical activity (PA) and socio-demographic and behavioral factors in Physical Education students. The sample was calculated considering the course, licentiate and bachelor, being composed by 217 students (54,8% male). For the evaluation of SBC, Marcus et al questionnaire was used. The PA behavior was dichotomized in active and inactive. Analyzed socio-demographic variables were gender, age, economic level, marital status, paid work, mother?s education and course. Health-related behavior was analyzed through health and nutrition self-perception. Poisson?s Regression was used to examine the association between the Stages of Behavior Change (SBC) for physical activity (PA) and socio-demographic and behavioral factors, considering p=0,05. Great part of the students were at the maintenance stage (38,7%). The prevalence of inactive behavior between the students (precontemplation, contemplation and preparation stages) was 45,2%. Results on the adjusted analysis have indicated that female students (PR: 1,64; CI 95%: 1,21-2,23) present higher probabilities to have an inactive behavior comparing to male. Mother?s education lower than nine years was a protection factor to present an inactive behavior (PR: 0,66; CI 95%: 0,45-0,99). These fi ndings may be useful for the development of health-promotion programs, in the university, withspecial attention to female gender students with high mother?s education.