Brazil Nut (Bertholletia excelsa) Beverage Processed by High-Pressure Homogenization: Changes in Main Components and Antioxidant Capacity during Cold Storage.

High-pressure homogenization (HPH) is an emerging technology for obtaining physical and microbial stability of plant-based milks, but there is little information on the effects of this technology on the phytochemical components of the processed plant food beverage and during its cold storage. The effect of three selected HPH treatments (180 MPa/25 °C, 150 MPa/55 °C, and 50 MPa/75 °C) and pasteurization (PAS) (63 °C, 20 min) on minor lipid constituents, total proteins, phenolic compounds, antioxidant capacity, and essential minerals of Brazil nut beverage (BNB) were studied. Additionally, the study of the possible changes in these constituents was carried out during cold storage at 5 °C for 21 days. The fatty acid profile (dominated by oleic acid and linoleic acid), free fatty acid content, protein, and essential minerals (notable source of Se and Cu) of the processed BNB remained almost stable to treatments (HPH and PAS). Specifically, reductions in squalene (22.7 to 26.4%) and γ-γ-tocopherol (28.4 to 36%) were observed in beverages processed via both non-thermal HPH and thermal PAS, but ß-sitosterol remained unchanged. Total phenolics were reduced (24 to 30%) after both treatments, a factor that influenced the observed antioxidant capacity. The studied individual phenolics in BNB were gallic acid, catechin, epicatechin, catechin gallate, and ellagic acid, being the most abundant compounds. During cold storage (5 °C) up to 21 days, changes in the content of phytochemicals, minerals, and total proteins were not noticeable for any treated beverages, and no lipolysis processes were promoted. Therefore, after the application of HPH processing, Brazil nut beverage (BNB) maintained almost unaltered levels of bioactive compounds, essential minerals, total protein, and oxidative stability, remarkable characteristics for its potential development as a functional food.

Acromegalia por macroadenoma hipofisiario en paciente con síndrome de McCune-Albright. Reporte de caso y revisión de la literatura / Acromegaly due to pituitary macroadenoma in a patient with McCune-Albright syndrome. Case report and literature overview

Introducción: El síndrome de McCune-Albright (SMA) es una enfermedad rara caracterizada por la triada: manchas cutáneas de color café con leche, displasia fibrosa poliostótica y pubertad precoz. Puede afectar a diversos ejes hormonales, entre ellos el de la hormona de crecimiento (GH), pudiendo asociarse a acromegalia. Reporte de caso: describimos el caso de una mujer de 44 años, con pubertad precoz periférica, hemorragia uterina anormal, crecimiento de manos y pies, prognatismo, prominencia frontal, manchas café con leche y tumoraciones pétreas en cara y antebrazos. Resultados: Apoyados con exámenes laboratoriales y de imágenes, se llegaron a los diagnósticos de acromegalia, hipogonadismo hipogonadotropo y síndrome de McCune-Albright. La paciente fue sometida a tratamiento quirúrgico con persistencia de enfermedad clínica y laboratorial. Conclusión: El diagnóstico y tratamiento oportunos de la acromegalia y sus complicaciones brindará un mejor pronóstico a los pacientes con SMA.

Background: McCune-Albright syndrome (MAS) is a rare disease characterized by the triad: café-au-lait skin spots, polyostotic fibrous dysplasia, and precocious puberty. It can affect various hormonal axes, including growth hormone (GH), and may be associated with acromegaly. We describe the case Case report:of a 44-year-old woman with peripheral precocious puberty, abnormal uterinebleeding, growthof thehands and feet, prognathism, frontal prominence, café-au-lait spots, and stony tumorsonthefaceandforearms.Supportedby Results:laboratory and imaging tests, the diagnoses of acromegaly, hypogonadotropic hypogonadism and McCune-Albright syndrome were reached. The patient underwent surgical treatment with persistence of clinical and laboratory disease. Conclusion: Timely diagnosis and treatment of acromegaly and its complications will provide a better prognosis for patients with MAS

Composition of Brazil Nut (Bertholletia excels HBK), Its Beverage and By-Products: A Healthy Food and Potential Source of Ingredients.

The consumption of plant-based beverages is a growing trend and, consequently, the search for alternative plant sources, the improvement of beverage quality and the use of their by-products, acquire great interest. Thus, the purpose of this work was to characterize the composition (nutrients, phytochemicals and antioxidant activity) of the Brazil nut (BN), its whole beverage (WBM), water-soluble beverage (BM-S), and its by-products of the beverage production: cake, sediment fraction (BM-D), and fat fraction (BM-F). In this study, advanced methodologies for the analysis of the components were employed to assess HPLC-ESI-QTOF (phenolic compounds), GC (fatty acids), and MALDI-TOF/TOF (proteins and peptides). The production of WBM was based on a hot water extraction process, and the production of BM-S includes an additional centrifugation step. The BN showed an interesting nutritional quality and outstanding content of unsaturated fatty acids. The investigation found the following in the composition of the BN: phenolic compounds (mainly flavan-3-ols as Catechin (and glycosides or derivatives), Epicatechin (and glycosides or derivatives), Quercetin and Myricetin-3-O-rhamnoside, hydroxybenzoic acids as Gallic acid (and derivatives), 4-hydroxybenzoic acid, ellagic acid, Vanillic acid, p-Coumaric acid and Ferulic acid, bioactive minor lipid components (ß-Sitosterol, γ-Tocopherol, α-Tocopherol and squalene), and a high level of selenium. In beverages, WBM had a higher lipid content than BM-S, a factor that influenced the energy characteristics and the content of bioactive minor lipid components. The level of phenolic compounds and selenium were outstanding in both beverages. Hydrothermal processing can promote some lipolysis, with an increase in free fatty acids and monoglycerides content. In by-products, the BM-F stood out due to its bioactive minor lipid components, the BM-D showed a highlight in protein and mineral contents, and the cake retained important nutrients and phytochemicals from the BN. In general, the BN and its beverages are healthy foods, and its by-products could be used to obtain healthy ingredients with appreciable biological activities (such as antioxidant activity).

Validación por especialistas de un grupo de ejercicios pliométricos de fuerza-reactiva para futbolistas de la categoría sub-14 / Validação por especialistas de um grupo de exercícios pliométricos de força-reativa para jogadores de futebol sub-14 / Validation by specialists of a reactive-strength plyometric exercises group for U-14 Soccer players

RESUMEN La pliometría es un método de entrenamiento diseñado para reproducir movimientos rápidos, explosivos y potentes; mejora la fuerza y la rapidez en distintos planos musculares, por lo cual suele ser muy útil para mejorar ciertas habilidades físicas en deportes como el fútbol. El objetivo de esta investigación es validar teóricamente, mediante consulta por especialistas, un grupo de ejercicios pliométricos de fuerza-reactiva para futbolistas categoría sub-14. Esta investigación es de tipo descriptiva-explicativa, de orden cualitativa y correlacional. Se encuestan a 21 especialistas de fútbol, clasificados en dos grupos independientes, se validan teóricamente alcances y limitaciones de una propuesta de ejercicios pliométricos para miembros inferiores, adaptados a futbolistas sub-14. Los promedios que describen los puntajes alcanzados fueron mayores en el postest, existen diferencias significativas al evaluar indistintamente cada grupo estudiado (Grupo 1: "I" r=0.004, "A" r=0.005, "P" r=0.003, "V" r=0.003 y "EP" r=0.003; Grupo 2: "I" r=0.002, "A" r=0.003, "P" r=0.001, "V" r=0.003 y "EP" r=0.002), no existen diferencias significativas al comparar los resultados entre cada grupo independiente como parte del pretest "I" (p=0.973), "A" (p=0.756), "P" (p=0.426), "V" (p=1.000) y "EP" (p=0.468) y como parte del postest "I" (p=0.223), "A" (p=0.973), "P" (p=0.173), "V" (p=0.918) y "EP" (p=0.918). Con este trabajo, se mejora teóricamente la propuesta de intervención, concerniente en 25 ejercicios de pliometría aplicada a miembros inferiores de futbolistas sub-14, además, se tienen presente cinco indicadores de análisis. Se recomienda realizar una validación práctica que enfoque la investigación a futuro, con un tipo de investigación experimental o cuasi-experimental.

RESUMO A Pliometria é um método de treino concebido para reproduzir movimentos rápidos, explosivos e poderosos; melhora a força e a rapidez em diferentes planos musculares, pelo que é normalmente muito útil para melhorar certas capacidades físicas em desportos como o futebol. O objetivo desta investigação é validar teoricamente, através da consulta por especialistas, um grupo de exercícios pliométricos de força reativa para jogadores de futebol sub-14. Esta investigação é descritiva-explicativa, qualitativa e correlacional. Vinte e um especialistas em futebol, classificados em dois grupos independentes, foram inquiridos. O âmbito e as limitações de uma proposta de exercícios pliométricos para membros inferiores, adaptados aos jogadores de futebol sub-14, foram teoricamente validados. As médias que descrevem as pontuações obtidas foram mais elevadas no pós-teste, existem diferenças significativas ao avaliar indistintamente cada grupo estudado (Grupo 1: "I" r=0. 004, "A" r=0,005, "P" r=0,003, "V" r=0,003 e "EP" r=0,003; Grupo 2: "I" r=0,002, "A" r=0,003, "P" r=0,001, "V" r=0,003 e "EP" r=0. 002), não há diferenças significativas ao comparar os resultados entre cada grupo independente como parte do "I" (p=0,973), "A" (p=0). 756), "P" (p=0,426), "V" (p=1.000) e "EP" (p=0,468) e como parte do pós-teste "I" (p=0,223), "A" (p=0,973), "P" (p=0,173), "V" (p=0,918) e "EP" (p=0,918). Com este trabalho, a proposta de intervenção é teoricamente melhorada, relativamente a 25 exercícios pliométricos aplicados aos membros inferiores dos jogadores de futebol sub-14, além disso, são tidos em conta cinco indicadores de análise. Recomenda-se a realização de uma validação prática que focalize a investigação futura, com um tipo de investigação experimental ou quase-experimental.

ABSTRACT Plyometry is a training method designed to reproduce fast explosive and powerful movements, it improves strength and speed in different muscle planes, which is why it is usually very useful to improve certain physical skills in sports such as soccer. The objective of this research is to theoretically validate, through consultation with specialists, a group of plyometric strength-reactive exercises for U-14 soccer players. This is a qualitative and correlational descriptive-explanatory research. Twenty-one soccer specialists classified into two independent groups were surveyed, theoretically validating the scope and limitations of a plyometric exercises proposal for lower limbs adapted to U-14 soccer players. The averages that describe the scores achieved were higher in the post-test, with significant differences when evaluating each group studied (Group 1: "I" r=0.004, "A" r=0.005, "P" r=0.003, " V "r=0.003 and" EP "r=0.003; Group 2:" I "r=0.002," A"r=0.003," P "r=0.001," V "r=0.003 and" EP "r=0.002), there is not significant differences when comparing the results between each independent group as part of the pretest "I" (p = 0.973), "A" (p = 0.756), "P" (p = 0.426), "V" (p = 1.000) and "EP" (p = 0.468), and as part of the post-test "I" (p = 0.223), "A" (p = 0.973), "P" (p = 0.173), "V" (p = 0.918) and "EP" (p = 0.918). With this work, the intervention proposal is theoretically improved, concerning 25 plyometric exercises applied to lower limbs of U-14 soccer players, in addition, five analysis indicators are taken into account. It is recommended to carry out a practical validation that focuses future research, with a type of experimental or quasi-experimental research.

Biodegradation of biodiesel-oil by Cellulosimicrobium sp. Isolated from Colombian Caribbean soils.

Biodiesel is considered to be a natural substitute for fossil fuel. The comparatively low toxicity of biodiesel and its susceptibility to microbial biodegradation could reduce its environmental impact. Currently, biodiesel is sold previously mixed with petroleum-based hydrocarbons. The aim of this work was to measure the biodegradation potential of commercially available biodiesel, using bacterial strains (BBCOL-001, BBCOL-002, and BBCOL-003) isolated from a tropical forest soils in the Colombian Caribbean. According to nucleotide sequencing of the gene encoding for 16S rRNA, the strains belong to members of the genus Cellulosimicrobium. GC-MS analysis showed that biodiesel-oil alkanes were degraded by an average of 81.5% with optical density reaching 0.2-0.3 in minimal salt media at 37°C for 5 days. Individual diesel-oil alkanes were degraded by the strains at rates between 64.9% to 100%. The increase in bacterial biomass confirmed the use of the substrates by the microorganisms, suggesting these hydrocarbons are a carbon source. Changes in the biochemical behaviour of the strains suggested their capacity to adapt to environmental conditions might be an important resource for bioremediation.

A molecular docking study of the interactions between human transferrin and seven metallocene dichlorides.

Human Transferrin (hTf) is a metal-binding protein found in blood plasma and is well known for its role in iron delivery. With only a 30% of its capacity for Fe+3 binding, this protein has the potential ability to transport other metal ions or organometallic compounds from the blood stream to all cell tissues. In this perspective, recent studies have described seven metallocene dichlorides (Cp2M(IV)Cl2, M(IV)=V, Mo, W, Nb, Ti, Zr, Hf) suitable as anticancer drugs and less secondary effects than cisplatin. However, these studies have not provided enough data to clearly explain how hTf binds and transports these organometallic compounds into the cells. Thus, a computational docking study with native apo-hTf using Sybyl-X 2.0 program was conducted to explore the binding modes of these seven Cp2M(IV)Cl2 after their optimization and minimization using Gaussian 09. Our model showed that the first three Cp2M(IV)Cl2 (M(IV)=V, Mo, W) can interact with apo-hTf on a common binding site with the amino acid residues Leu-46, Ile-49, Arg-50, Leu-66, Asp-69, Ala-70, Leu-72, Ala-73, Pro-74 and Asn-75, while the next four Cp2M(IV)Cl2 (M(IV)=Nb, Ti, Zr, Hf) showed different binding sites, unknown until now. A decreasing order in the total score (equal to -log Kd) was observed from these docking studies: W (5.4356), Mo (5.2692), Nb (5.1672), V (4.5973), Ti (3.6529), Zr (2.0054) and Hf (1.8811). High and significant correlation between the affinity of these seven ligands (metallocenes) for apo-hTf and their bond angles CpMCp (r=0.94, p<0.01) and Cl-M-Cl (r=0.95, p<0.01) were observed, thus indicating the important role that these bond angles can play in ligand-protein interactions. Fluorescence spectra of apo-hTf, measured at pH 7.4, had a decrease in the fluorescence emission spectrum with increasing concentration of Cp2M(IV)Cl2. Experimental data has a good correlation between KA (r=0.84, p=0.027) and Kd (r=0.94, p=0.0014) values and the calculated total scores obtained from our docking experiments. In conclusion, these results suggest that the seven Cp2M(IV)Cl2 used for this study can interact with apo-hTf, and their affinity was directly and inversely proportional to their bond angles CpMCp and ClMCl, respectively. Our docking studies also suggest that the binding of the first three Cp2M(IV)Cl2 (M(IV)=V, Mo, W) to hTf could abrogate the formation of the hTf-receptor complex, and as a consequence the metallocene-hTf complex might require another transport mechanism in order to get into the cell.

Amlodipino y choque vasodilatado en una unidad de cuidados intensivos de un hospital general: Reporte de caso / Amlodipine and vasodilated shock in an intensive care unit of a general hospital: Case report

Los calcio antagonistas son fármacos usados para diferentes patologías médicas; sin embargo la intoxicación puede ser grave. Presentamos el caso de una mujer joven intoxicada por amlodipino quien cursó con choque vasodilatado y disfunción multiorgánica, en quien se usó vasopresores múltiples a dosis por encima de las habituales para estabilizarla. (AU)

Calcium antagonists are used in a number of medical conditions, but intoxication with these drugs may be lethal.We present the case of a young women intoxicated with amlodipine who presented with vasodilated shock and multi organ disfunction in whom multiple vasopressors at maximum allowed doses were used to estabilize the patient. (AU)

Fiebre amarilla y disfunción multiorgánica: Reporte de tres casos / Yellow fever and multi organ dysfunction: Report of three cases

Fiebre amarilla es una enfermedad viral aguda causada por un virus de la familia Flaviviridae transmitida por vectores, caracterizada por síndrome ictérico febril hemorrágica y que puede cursar con disfunción multiorgánica, con alta mortalidad. Se reportan tres casos de pacientes que viajaron a La Merced, Chanchamayo, que cursaron con síndrome ictérico febril hemorrágico con disfunción multiorgánica, con diagnóstico serológico de fiebre amarilla; uno sobrevivió y dos fallecieron. (AU)

Yellow fever is a vector-borne disease caused by a virus of the Flaviviridae family that is characterized by fever and jaundice that may progressed to multi organ failure with high associated mortality. We report three cases of patients who had travelled to La Merced, Chanchamayo who presented with multi organ failure with confirmed serology for yellow fever, one survived and the other two died. (AU)

Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors.

Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (http://www.msdiscovery.com/natprod.html), with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (-10.7), HER2-hecogenin acetate (-11.2), HER3-hesperidin (-11.5) and HER4-theaflavin (-10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC50 values followed a significant linear relationship with the theoretical binding Affinity data for HER1 (R = 0.656, p < 0.0001) and HER2 (R = 0.543, p < 0.0001), but not for HER4 (R = 0.364, p > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs.

Acidosis láctica y choque distributivo por sobredosis de metformina: Reporte de caso / Lactic acidosis and distributive shock due to metformin overdose: Case report

Metformina es una biguanida usada como agente antihiperglicemiante, que promueve la euglicemia; su principal toxicidad es acidosis láctica. Se reporta el caso de un varón, adulto mayor, diabético e hipertenso quien se automedicó con 10 tabletas de metformina 850 mg; presentando acidosis láctica severa y choque distributivo requiriendo soporte y manejo en la Unidad de Cuidados Intensivos. (AU)

Metformin is a biguanide drug used as an oral antidiabetic medication whose main toxicity is lactic acidosis. We report the case of an old adult male diabetic and hypertensive patient who self prescribed 10 tablets of metformin 850mg presenting lactic acidosis and distributive shock requiring treatment in the intensive care unit. (AU)

Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach.

Human Cytochrome P450s (CYP450) are a group of heme-containing metalloenzymes responsible for recognition and metabolism of numerous xenobiotics, including drugs and environmental contaminants. CYP2B6, a member of CYP450, is well known for being a highly inducible and polymorphic enzyme and for its important role in the oxidative metabolism of environmental pollutants, such as the Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). However the mechanisms of interaction of PBDEs and PCBs with CYP2B6 is not entirely known. In this work, a computational approach was carried out to study the interactions of 41 POPs (17 PBDEs, 17 PCBs, and 7 Dioxins) with four CYP2B6 protein structures downloaded from PDB data base (PDB: 3UA5, 3QOA, 3QU8 and 4I91) using molecular docking protocols with AutoDock Vina. The best binding affinity values (kcal/mol) were obtained for PBDE-99 (-8.5), PCB-187 (-9.6), and octachloro-dibenzo-dioxin (-9.8) that can be attributed to the hydrophobic interactions with important residues, such as Phe-363, in the catalytic site of CYP2B6. Molecular docking validation revealed the best values for PDB: 3UA5 (R = 0.622, p = 0.001) demonstrating the reliability of molecular docking predictions. The information obtained in this work can be useful in evaluating the modes of interaction of xenobiotic compounds with the catalytic site of CYP2B6 and provide insights on the important role of these enzymes in the metabolism of potentially toxic compounds in humans.

Discovery of antiviral molecules for dengue: In silico search and biological evaluation.

BACKGROUND: Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. METHODS: NS2B/NS3 protease complex structural information was employed to find small molecules that are capable of inhibiting the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrate and the complex NS2B/NS3 obtained by recombinant DNA techniques. HepG2 cells infected with dengue virus serotype 2 were used to test the activity against dengue virus replication. RESULTS: A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that were capable of inhibiting this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. CONCLUSIONS: Chemicals CID 54681617, CID 54692801 and CID 54715399 were strong inhibitors of NS2B/NS3, with IC50 values (µM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9%, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. GENERAL SIGNIFICANCE: This discovery opens new possibilities for obtaining drug candidates against Dengue virus.

Computational fishing of new DNA methyltransferase inhibitors from natural products.

DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs. In order to find NPs with novel chemotypes as DNMTis, 47 compounds with known activity against these enzymes were used to build a LDA-based QSAR model for active/inactive molecules (93% accuracy) based on molecular descriptors. This classifier was employed to identify potential DNMTis on 800 NPs from NatProd Collection. 447 selected compounds were docked on two human DNA methyltransferase (DNMT) structures (PDB codes: 3SWR and 2QRV) using AutoDock Vina and Surflex-Dock, prioritizing according to their score values, contact patterns at 4 Å and molecular diversity. Six consensus NPs were identified as virtual hits against DNMTs, including 9,10-dihydro-12-hydroxygambogic, phloridzin, 2',4'-dihydroxychalcone 4'-glucoside, daunorubicin, pyrromycin and centaurein. This method is an innovative computational strategy for identifying DNMTis, useful in the identification of potent and selective anticancer drugs.

Water soluble molybdenocene complexes: synthesis, cytotoxic activity and binding studies to ubiquitin by fluorescence spectroscopy, circular dichroism and molecular modeling.

Four new molybdenocene complexes, Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato), [Cp2Mo(ethyl maltolato)]Cl and Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato), were synthesized and structurally characterized by standard analytical methods. The cytotoxicity of these complexes was assessed on colon HT-29 and breast MCF-7 cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A higher cytotoxic activity was shown by all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex. The complexes Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato) and [Cp2Mo(ethyl maltolato)]Cl displayed a stronger cytotoxic activity on colon cancer HT-29 cell line, over the molybdenocene dichloride (Cp2MoCl2). In contrast, Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato) exhibited proliferative properties on this cell line. Ubiquitin (Ub)-molybdenocene interactions were investigated using cyclic voltammetry, fluorescence quenching spectroscopy, circular dichroism (CD) and molecular modeling. The thermodynamic parameters (ΔH and ΔS) obtained using fluorescence quenching spectra and van't Hoff plot indicate the Ub-molybdenocene interactions are mainly hydrophobic. The CD data also support hydrophobic interactions with conformational changes in the Ub protein. Docking studies using molecular modeling revealed the amino acids involved in the Ub-molybdenocene interactions and corroborated the hydrophobic nature of the binding combined with hydrogen bonding.

Food-related compounds that modulate expression of inducible nitric oxide synthase may act as its inhibitors.

Natural compounds commonly found in foods may contribute to protect cells against the deleterious effects of inflammation. These anti-inflammatory properties have been linked to the modulation of transcription factors that control expression of inflammation-related genes, including the inducible nitric oxide synthase (iNOS), rather than a direct inhibitory action on these proteins. In this study, forty two natural dietary compounds, known for their ability to exert an inhibitory effect on the expression of iNOS, have been studied in silico as docking ligands on two available 3D structures for this protein (PDB ID: 3E7G and PDB ID: 1NSI). Natural compounds such as silibinin and cyanidin-3-rutinoside and other flavonoids showed the highest theoretical affinities for iNOS. Docking affinity values calculated for several known iNOS inhibitors significatively correlated with their reported half maximal inhibitory concentrations (R = 0.842, P < 0.0001), suggesting the computational reliability of the predictions made by our docking simulations. Moreover, docking affinity values for potent iNOS inhibitors are of similar magnitude to those obtained for some studied natural products. Results presented here indicate that, in addition to gene expression modulation of proteins involved in inflammation, some chemicals present in food may be acting by direct binding and possible inhibiting actions on iNOS.

Potential interaction of natural dietary bioactive compounds with COX-2.

Bioactive natural products present in the diet play an important role in several biological processes, and many have been involved in the alleviation and control of inflammation-related diseases. These actions have been linked to both gene expression modulation of pro-inflammatory enzymes, such as cyclooxygenase 2 (COX-2), and to an action involving a direct inhibitory binding on this protein. In this study, several food-related compounds with known gene regulatory action on inflammation have been examined in silico as COX-2 ligands, utilizing AutoDock Vina, GOLD and Surflex-Dock (SYBYL) as docking protocols. Curcumin and all-trans retinoic acid presented the maximum absolute AutoDock Vina-derived binding affinities (9.3 kcal/mol), but genistein, apigenin, cyanidin, kaempferol, and docosahexaenoic acid, were close to this value. AutoDock Vina affinities and GOLD scores for several known COX-2 inhibitors significatively correlated with reported median inhibitory concentrations (R² = 0.462, P < 0.001 and R² = 0.238, P = 0.029, respectively), supporting the computational reliability of the predictions made by our docking simulations. Moreover, docking analysis insinuate the synergistic action of curcumin on celecoxib-induced inhibition of COX-2 may occur allosterically, as this natural compound docks to a place different from the inhibitor binding site. These results suggest that the anti-inflammatory properties of some food-derived molecules could be the result of their direct binding capabilities to COX-2, and this process can be modeled using protein-ligand docking methodologies.