Toxicogenomics of the C-C chemokine receptor type 5 (CCR5): Exploring the potential impacts of chemical-CCR5 interactions on inflammation and human health.

This article explores the impact of environmental chemicals on CCR5 expression and related inflammatory responses based on curated data from the Comparative Toxicogenomics Database (CTD). A total of 143 CCR5-interacting chemicals was found, with 229 chemical interactions. Of note, 67 (29.3%) out of 229 interactions resulted in "increased expression" of CCR5 mRNA or CCR5 protein, and 42 (18.3%) chemical interactions resulted in "decreased expression". The top-5 CCR5-interacting chemicals were "Tetrachlorodibenzodioxin", "Lipopolysaccharides", "Benzo(a)pyrene", "Drugs, Chinese Herbal", and "Ethinyl Estradiol". Based on the number of interactions and importance as environmental contaminant, we then focused our analysis on Tetrachlorodibenzodioxin and Benzo(a)pyrene. There is some consistency in the data supporting an increase in CCR5 expression triggered by Tetrachlorodibenzodioxin; although data concerning CCR5-Benzo(a)pyrene interactions is limited. Considering the high linkage disequilibrium between CCR5 and CCR2 genes, we also search for chemicals that interact with both genes, which resulted in 72 interacting chemicals, representing 50.3% of the 143 CCR5-interacting chemicals and 37.5% of the 192 CCR2-interacting chemicals. In conclusion, CTD data showed that environmental contaminants indeed affect CCR5 expression, with a tendency towards increased expression. The interaction of environmental contaminants with other chemokine receptor genes may potentialize their toxic effects on the chemokine system, favoring inflammation.

Examining the paradox of urban disease ecology by linking the perspectives of Urban One Health and Ecology with Cities.

The ecology of zoonotic, including vector-borne, diseases in urban social-ecological systems is influenced by complex interactions among human and environmental factors. Several characteristics contribute to the emergence and spread of infectious diseases in urban places, such as high human population densities, favorable habitat for vectors, and humans' close proximity to animals and their pathogens. On the other hand, urban living can contribute to the improvement of public health through better access to health services and creation of ecological and technological infrastructure that reduces disease burdens. Therefore, urbanization creates a disease ecology paradox through the interplay of urban health penalties and advantages for individual and community outcomes. To address this contradiction, we advocate a holistic Urban One Health perspective for managing urban systems, especially their green spaces and animal populations, in ways that more effectively control the spread of zoonotic diseases. This view should be coupled with an Ecology with Cities approach which emphasizes actionable science needed for urban planning, management and policymaking; developing disease and vector surveillance programs using citizen and community science methods; and improving education and communication actions that help diverse stakeholders understand the complexities of urban disease ecology. Such measures will enable scholars from many disciplines to collaborate with professionals, government officials, and others to tackle challenges of the urban disease paradox and create more sustainable, health-promoting environments.

Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases.

One of the most striking characteristics of human beings is the incredible capacity to adapt to different environments. This capacity allowed humans to spread all over our planet, occupying habitats as diverse as deserts, tropical forests or tundra regions. Interactions with the environment, climate, food and water availability shaped our evolution and define our survival. Essential to human life, oxygen availability also controls human dispersion and adaptation. For example, low oxygen availability can lead to physiological adaptations in populations living in highlands. Moreover, the consequences of differential oxygen availability (or even exposure to hypoxia) are evident in process as fine-tuned controlled as gene regulation. Physiological responses to fluctuations in oxygen availability are crucial already from the early days of life, since the human fetal environment is characterized by hypoxia. Hypoxia-Inducible Factors (HIFs) act as major regulators of pathways involved in glycolysis, erythropoiesis, angiogenesis, cell proliferation and stem cells function. Here we explore the physiological consequences of hypoxia in the human organism. In this sense, and considering the existence of HIF sequences in promoter regions of genes important to immune regulation, we hypothesize that exposure to induced hypoxia through the use of hypobaric chambers can be used as a complementary therapy to control chronic inflammation in several diseases characterized by systemic inflammatory conditions. Among these inflammatory conditions we highlight autoimmune diseases and chronic inflammation in HIV infected individuals under antiretroviral treatment. Several experiments, including arthritis animal models, the evaluation of athletes that already use hypobaric chambers to induce erythropoiesis, and the potential consequences of hypoxia as an immunotolerogenic inducer in the HIV infection context are approached and discussed here.

Wound healing and anti-inflammatory activities induced by a Plantago australis hydroethanolic extract standardized in verbascoside.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantago australis is a popular plant found to be widely spread in Latin America. In folk medicine, the seeds and leaves are used mainly for anti-inflammatory, wound healing, among others. The verbascoside, a phenolic glycoside, is an active chemical component described in this species of plant, which has antioxidant, anti-inflammatory and healing effects. PURPOSE: The aim of the present study was to evaluate whether P. australis hydroethanolic extract (PAHE) standardized in verbascoside could promote wound healing associated with anti-inflammatory action within both in vitro and in vivo models. METHODS: For the wound healing activity, we used a Scratch Test, an assay capable of evaluating the migratory ability of keratinocyte cells (HaCat) in vitro and thereby confirming the activity in rats. For the anti-inflammatory activity, the inflammation was induced with LPS in microglial murine cells (N9). Inflammatory mediators (IL-6, IL-10, IL-12p70, INFγ, MCP-1 and TNFα) were measured and the activity of superoxide dismutase (SOD), catalase (CAT), and mitochondrial membrane potential were evaluated. In addition, using paw edema induced by carrageenan in rats, the anti-inflammatory activity in vivo was analyzed. RESULTS: The PAHE and verbascoside, induced a significant increase in migration of keratinocytes, at all concentrations tested when compared to the negative control. The wound healing activity in vivo showed that the PAHE accelerated the process. The treatments with PAHE and verbascoside induce increases in the antioxidants enzymes, suggesting a possible activation of these enzymes. However, this did not result in an increase in the expression of inflammatory mediators in microglial cells. In LPS activated cells the verbascoside displayed a significant reduction of TNFα, IL-6, IL-12p70, MCP-1 and INFγ, while the PAHE only displayed statistically significant reduction in TNFα. Interestingly, both the compounds could reduce the oxidative parameters in N9 cells activated by LPS. Additionally, pretreatment with PAHE inhibited the paw edema in rats. CONCLUSION: The results suggest that PAHE has wound healing activity, improving cells migration and, as well as was able to reverse the oxidation effect in LPS-activated N9 cells. The wound-healing and anti-inflammatory activities of PAHE were confirmed in vivo. In addition, the presence of verbascoside can be related to PAHE effects, since this compound was capable of increase keratinocytes migration and inhibiting inflammation mediators.

Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats.

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.