Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone.

Ozone (O3) is an oxidating tropospheric pollutant. When O3 interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O3. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O3 control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O3. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O3.

Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone.

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.

In silico analysis of missense mutations in exons 1-5 of the F9 gene that cause hemophilia B.

BACKGROUND: Missense mutations in the first five exons of F9, which encodes factor FIX, represent 40% of all mutations that cause hemophilia B. To address the ongoing debate regarding in silico identification of disease-causing mutations at these exons, we analyzed 215 missense mutations from www.factorix.org using six in silico prediction tools, which are the most common used programs for analysis prediction of impact of mutations on the protein structure and function, with further advantage of using similar approaches. We developed different algorithms to integrate multiple predictions from such tools. In order to approach a structural analysis on FIX we performed a modeling of five selected pathogenic mutations. RESULTS: SIFT, PolyPhen-2 HumDiv, SNAP2, and MutationAssessor were the most successful in identifying true non-causative and causative mutations. A proposed function integrating these algorithms (wgP4) was the most sensitive (90.1%), specific (22.6%), and accurate (87%) than similar functions, and identified 187 variants as deleterious. Clinical phenotype was significantly associated with predicted causative mutations at all five exons. However, PolyPhen-2 HumDiv was more successful in linking clinical severity to specific exons, while functions that integrate 4-6 predictions were more successful in linking phenotype to genotypes at the light chain (exons 3-5). The most important value of integrating multiple predictions is the inclusion of scores derived from different approaches. Modeling of protein structure showed the effects of pathogenic nsSNPs on structure and function of FIX. CONCLUSIONS: A simple function that integrates information from different in silico programs yields the best prediction of mutated phenotypes. However, the specificity, sensitivity, and accuracy of genotype-phenotype predictions depend on specific characteristics of the protein domain and the disease of interest as we validated by the structural analysis of selected pathogenic F9 mutations. The proposed function integrating algorithm (wgP4) might be useful for the analysis of nsSNPs impact on other genes.

Curcumin Exerted Neuroprotection against Ozone-Induced Oxidative Damage and Decreased NF-κB Activation in Rat Hippocampus and Serum Levels of Inflammatory Cytokines.

Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-κB can be activated in response to oxidative damage, inducing an inflammatory response. Nowadays, there are no reliable results that consolidate the use of antioxidants to protect from damage caused by ozone, particularly in highly polluted cities. Curcumin has a strong antioxidant activity and is a potent inhibitor of NF-κB activation with no side effects. The aim of this study is to evaluate the effect of curcumin in preventive and therapeutic approaches against oxidative damage, NF-κB activation, and the rise in serum levels of IL-1ß and TNF-α induced by acute and chronic exposure to ozone in rat hippocampus. One hundred male Wistar rats were distributed into five groups; the intact control, curcumin-fed control, the ozone-exposed group, and the preventive and therapeutic groups. These last two groups were exposed to ozone and received food supplemented with curcumin. Lipid peroxidation was determined by spectrophotometry, and protein oxidation was evaluated by immunodetection of carbonylated proteins and densitometry analysis. Activation of NF-κB was assessed by electrophoretic mobility shift assay (EMSA), and inflammatory cytokines (IL-1ß and TNF-α) were determined by ELISA. Curcumin decreased NF-κB activation and serum levels of inflammatory cytokines as well as protein and lipid oxidation, in both therapeutic and preventive approaches. Curcumin has proven to be a phytodrug against the damage caused by the environmental exposure to ozone.

Patented aptamers for C-reactive protein detection: a review about their use in clinical diagnostics.

C-reactive protein (CRP) is a homopentameric oligoprotein composed of monomeric subunits that are about 21 kD each. The form of detectable native CRP in validated assays was developed in 2007 and from that time has been considered as an excellent biomarker for peripheral artery disease and/or atherosclerosis, as well as a cardiovascular disease marker for risk prediction. The improvements in the detection of CRP levels could predict significantly the population that have increased risk of stroke being the modulation of CRP levels as a therapeutical outcome for prevention of cardiovascular diseases. Nowadays antibodies that specifically bind CRP, as monoclonal anti-CRP antibodies, are available from commercial sources. Aptamers are biomolecules conformed principally by RNA or DNA, able to adopt secondary structures that can bind to epitopes from oligopeptides or complete proteins. The sensitivity and accuracy of aptamers has let to consider them as more efficient to identify proteins than just antibodies. These properties have become the base for testing these molecules for different uses. A battery of patented aptamers has been developed for detecting and/or measuring CRP. In this sense, aptamers against CRP (CRP-apt) would help to modulate CRP physiological actions at systemic, tissue, cellular and molecular levels by using appropriate experimental designs. This kind of studies would lead to fully understand which systems are regulated by the protein, what disturbances are produced if the CRP is missing or overexpressed. Finally, we hallmark other applications of CRP in terms of patents for both basic and applied research.

The diagnostic and therapeutic importance of human growth hormone isoforms.

The study of human growth hormone isoforms has conduced to the elaboration of patents related to very important items: codifying and regulatory sequences, production of the protein at large-scale, modifications to prolong half-life as monomer, dimer and fusion protein for treatments directed to growth-associated diseases. The designs to identification and quantification of hGH are besides the formers establishing very important basis of patented sources that can be used for a specific and opportune diagnosis and treatment of biological abnormalities or undesirable effects when these growth hormones are involved.