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Padmaraju V.,Indian Central Food Technological Research Institute | Bhaskar J.J.,Indian Central Food Technological Research Institute | Prasada Rao U.J.S.,Indian Central Food Technological Research Institute | Salimath P.V.,Indian Central Food Technological Research Institute | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2011

Parkinson's disease (PD) is a neurodegenerative disease with multiple etiologies. Advanced glycation end products (AGEs) accumulate in the aging brain and could be one of the reasons for age-related diseases like PD. Oxidative stress also leads to the formation of AGEs and may be involved in neurodegeneration by altering the properties of proteins. α-Synuclein is involved in pathogenesis of PD and there are limited studies on the role of AGE-α-synuclein in neurodegeneration. We studied the aggregation and DNA binding ability of AGE-α-synuclein in vitro. α-Synuclein is glycated using methylglyoxal and formation of AGE-α-synuclein is characterized using fluorescence studies, intrinsic tyrosine fluorescence, and fructosamine estimation. The results indicated that AGE-α-synuclein aggregates into smaller globular-like aggregates compared to fibrils formed with native α-synuclein. Further, it is found that AGE-α-synuclein induced conformational changes in scDNA from B-form to B-C-A mixed conformation. Additionally, AGE-α-synuclein altered DNA integrity as evidenced by the melting temperature, ethidium bromide, and DNAse I sensitivity studies. AGE-α-synuclein converted biphasic Tm to higher monophasic Tm. The Tm of AGE-α-synuclein-scDNA complex is more than that of native α-synuclein-scDNA complex, indicating that AGE-α-synuclein stabilized the uncoiled scDNA. AGE-α-synuclein could stabilize the uncoiled scDNA, as shown by the decrease in the number of ethidium bromide binding molecules per base pair of DNA. DNAse I sensitive studies indicated that both AGE-α-synuclein-scDNA and α-synuclein- scDNA are resistant to DNAse I digestion. The relevance of these findings to neuronal cell death is discussed. © 2011 - IOS Press and the authors. All rights reserved.

Gavilan R.G.,University of Santiago de Compostela | Gavilan R.G.,Institute for Scientific Research and Technology Services INDICASAT | Zamudio M.L.,Instituto Nacional Of Salud | Martinez-Urtaza J.,University of Santiago de Compostela | Martinez-Urtaza J.,U.S. Center for Disease Control and Prevention
PLoS Neglected Tropical Diseases | Year: 2013

Vibrio parahaemolyticus is a foodborne pathogen that has become a public health concern at the global scale. The epidemiological significance of V. parahaemolyticus infections in Latin America received little attention until the winter of 1997 when cases related to the pandemic clone were detected in the region, changing the epidemic dynamics of this pathogen in Peru. With the aim to assess the impact of the arrival of the pandemic clone on local populations of pathogenic V. parahaemolyticus in Peru, we investigated the population genetics and genomic variation in a complete collection of non-pandemic strains recovered from clinical sources in Peru during the pre- and post-emergence periods of the pandemic clone. A total of 56 clinical strains isolated in Peru during the period 1994 to 2007, 13 strains from Chile and 20 strains from Asia were characterized by Multilocus Sequence Typing (MLST) and checked for the presence of Variable Genomic Regions (VGRs). The emergence of O3:K6 cases in Peru implied a drastic disruption of the seasonal dynamics of infections and a shift in the serotype dominance of pathogenic V. parahaemolyticus. After the arrival of the pandemic clone, a great diversity of serovars not previously reported was detected in the country, which supports the introduction of additional populations cohabitating with the pandemic group. Moreover, the presence of genomic regions characteristic of the pandemic clone in other non-pandemic strains may represent early evidence of genetic transfer from the introduced population to the local communities. Finally, the results of this study stress the importance of population admixture, horizontal genetic transfer and homologous recombination as major events shaping the structure and diversity of pathogenic V. parahaemolyticus. © 2013 Gavilan et al.

Cherigo L.,University of Panama | Lopez D.,Acharya Nagarjuna University | Lopez D.,Institute for Scientific Research and Technology Services INDICASAT | Martinez-Luis S.,Institute for Scientific Research and Technology Services INDICASAT
Marine Drugs | Year: 2015

Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding cassette (ABC) transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute lymphocytic leukemias. The overexpression of BCRP contributes to the resistance of several chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone, doxorubicin and daunorubicin. The Food and Drugs Administration has already recognized that BCRP is clinically one of the most important drug transporters, mainly because it leads to a reduction of clinical efficacy of various anticancer drugs through its ATP-dependent drug efflux pump function as well as its apparent participation in drug resistance. This review article aims to summarize the different research findings on marine natural products with BCRP inhibiting activity. In this sense, the potential modulation of physiological targets of BCRP by natural or synthetic compounds offers a great possibility for the discovery of new drugs and valuable research tools to recognize the function of the complex ABC-transporters. © 2015 by the authors; licensee MDPI.

Torres-Mendoza D.,Institute for Scientific Research and Technology Services INDICASAT | Torres-Mendoza D.,Acharya Nagarjuna University | Gonzalez Y.,Acharya Nagarjuna University | Gonzalez Y.,Institute for Scientific Research and Technology Services INDICASAT | And 6 more authors.
Molecules | Year: 2016

Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS) together with molecular modeling studies. Compounds 1-3 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF) and Interleukin (IL)-6 induced by lipopolysaccharide (LPS) in murine macrophages. © 2016 by the authors; licensee MDPI.

Lopez D.,Institute for Scientific Research and Technology Services INDICASAT | Lopez D.,Acharya Nagarjuna University | Cherigo L.,University of Panama | Spadafora C.,Institute for Scientific Research and Technology Services INDICASAT | And 2 more authors.
Chemistry Central Journal | Year: 2015

Background: Panama has an extensive mangrove area and it is one of the countries with the highest biodiversity in America. Mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in America. Given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. This study was designed to evaluate the potential of Pelliciera rhizophorae as a source of bioactive compounds. Results: The present investigation was undertaken to explore the possible antiparasitic potential and aα-glucosidase inhibition by compounds derived from the Panamanian mangrove Pelliciera rhizophorae. Bioassay-guided fractionation of the crude extract led to the isolation of ten chemical compounds: aα-amyrine (1), β-amyrine (2), ursolic acid (3), oleanolic acid (4), betulinic acid (5), brugierol (6) iso-brugierol (7), kaempferol (8), quercetin (9), and quercetrin (10). The structures of these compounds were established by spectroscopic analyses including APCI-HR-MS and NMR. Compounds 4 (IC50 = 5.3 μM), 8 (IC50 = 22.9 μM) and 10 (IC50 = 3.4 μM) showed selective antiparasitic activity against Leishmania donovani, while compounds 1 (IC50 = 19.0 μM) and 5 (IC50 = 18.0 μM) exhibited selectivity against Tripanosoma cruzi and Plasmodium falciparum, respectively. Moreover, compounds 1-5 inhibited aα-glucosidase enzyme in a concentration-dependent manner with IC50 values of 1.45, 0.02, 1.08, 0.98 and 2.37 μM, respectively. Their inhibitory activity was higher than that of antidiabetic drug acarbose (IC50 217.7 μM), used as a positive control. Kinetic analysis established that the five compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bind at the same site that acarbose in the human intestinal aα-glucosidase (PDB: 3TOP). Conclusions: Three groups of compounds were isolated in this study (triterpenes, flavonols and dithiolanes). Triterpenes and flavones showed activity in at least one bioassay (antiparasitic or aα-glucosidase). In addition, only the pentacyclic triterpenes exhibited a competitive type of inhibition against aα-glucosidase. © 2015 López et al.

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