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1.
Proc Biol Sci ; 291(2020): 20232768, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38565154

ABSTRACT

Prior research on metacommunities has largely focused on snapshot surveys, often overlooking temporal dynamics. In this study, our aim was to compare the insights obtained from metacommunity analyses based on a spatial approach repeated over time, with a spatio-temporal approach that consolidates all data into a single model. We empirically assessed the influence of temporal variation in the environment and spatial connectivity on the structure of metacommunities in tropical and Mediterranean temporary ponds. Employing a standardized methodology across both regions, we surveyed multiple freshwater taxa in three time periods within the same hydrological year from multiple temporary ponds in each region. To evaluate how environmental, spatial and temporal influences vary between the two approaches, we used nonlinear variation partitioning analyses based on generalized additive models. Overall, this study underscores the importance of adopting spatio-temporal analytics to better understand the processes shaping metacommunities. While the spatial approach suggested that environmental factors had a greater influence, our spatio-temporal analysis revealed that spatial connectivity was the primary driver influencing metacommunity structure in both regions. Temporal effects were equally important as environmental effects, suggesting a significant role of ecological succession in metacommunity structure.


Subject(s)
Fresh Water , Ponds , Climate , Spatio-Temporal Analysis , Ecosystem
2.
J Appl Microbiol ; 135(1)2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38140942

ABSTRACT

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.


Subject(s)
Escherichia coli , beta-Lactamase Inhibitors , beta-Lactamase Inhibitors/pharmacology , Staphylococcus aureus/metabolism , Molecular Docking Simulation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , beta-Lactams/pharmacology , Microbial Sensitivity Tests , beta-Lactamases/genetics , beta-Lactamases/metabolism
3.
Chem Biodivers ; 21(2): e202301871, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38320175

ABSTRACT

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.


Subject(s)
Diospyros , Pesticides , Animals , Molecular Docking Simulation , Diospyros/chemistry , Diospyros/metabolism , Acetylcholinesterase/metabolism , Spodoptera , Pentacyclic Triterpenes
4.
Int J Mol Sci ; 25(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38673967

ABSTRACT

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.


Subject(s)
Antineoplastic Agents , Curcumin , Curcumin/analogs & derivatives , Magnesium , beta-Cyclodextrins , beta-Cyclodextrins/chemistry , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/pharmacokinetics , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Magnesium/chemistry , Apoptosis/drug effects , Female , Cell Line, Tumor , STAT3 Transcription Factor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Cell Movement/drug effects , Solubility , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Chick Embryo , Matrix Metalloproteinase 9/metabolism
5.
J Environ Manage ; 357: 120715, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38579465

ABSTRACT

The effluents from conventional wastewater treatment plants (WWTP), even if accomplishing quality regulations, substantially differ in their characteristics with those of waters in natural environments. Constructed wetlands (CWs) serve as transitional ecosystems within WWTPs, mitigating these differences and restoring natural features before water is poured into the natural environment. Our study focused on an experimental surface-flow CW naturalizing the WWTP effluent in a semiarid area in Eastern Spain. Despite relatively low pollutant concentrations entering the CW, it effectively further reduced settled organic matter and nitrogen. Dissolved organic matter (DOM) reaching the CW was mainly protein-like, yet optical property changes in the DOM indicated increased humification, aromaticity, and stabilization as it flowed through the CW. Flow cytometry analysis revealed that the CW released less abundant but more active bacterial populations than those received. MiSeq Illumina sequencing highlighted changes in the prokaryotic community composition, with phyla Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria dominating the CW outflow. Functional prediction tools (FaproTax and PICRUSt2) demonstrated a shift towards microbial guilds aligned with those of the natural aquatic environments, increased aerobic chemoheterotrophs, photoautotrophs, and metabolic reactions at higher redox potentials. Enhanced capabilities for degrading plant material correlated well with changes in the DOM pool. Our findings emphasize the role of CWs in releasing biochemically stable DOM and functionally suited microbial populations for natural receiving environments. Consequently, we propose CWs as a naturalization nature-based solution (NBS) in water-scarce regions like the Mediterranean, where reclaimed discharged water can significantly contribute to ecosystem's water resources compared to natural flows.


Subject(s)
Wastewater , Wetlands , Ecosystem , Citizenship , Bacteria , Dissolved Organic Matter , Mediterranean Region , Waste Disposal, Fluid
6.
BMC Biol ; 20(1): 175, 2022 08 08.
Article in English | MEDLINE | ID: mdl-35941649

ABSTRACT

BACKGROUND: Cyanobacteria are the major prokaryotic primary producers occupying a range of aquatic habitats worldwide that differ in levels of salinity, making them a group of interest to study one of the major unresolved conundrums in aquatic microbiology which is what distinguishes a marine microbe from a freshwater one? We address this question using ecogenomics of a group of picocyanobacteria (cluster 5) that have recently evolved to inhabit geographically disparate salinity niches. Our analysis is made possible by the sequencing of 58 new genomes from freshwater representatives of this group that are presented here, representing a 6-fold increase in the available genomic data. RESULTS: Overall, freshwater strains had larger genomes (≈2.9 Mb) and %GC content (≈64%) compared to brackish (2.69 Mb and 64%) and marine (2.5 Mb and 58.5%) isolates. Genomic novelties/differences across the salinity divide highlighted acidic proteomes and specific salt adaptation pathways in marine isolates (e.g., osmolytes/compatible solutes - glycine betaine/ggp/gpg/gmg clusters and glycerolipids glpK/glpA), while freshwater strains possessed distinct ion/potassium channels, permeases (aquaporin Z), fatty acid desaturases, and more neutral/basic proteomes. Sulfur, nitrogen, phosphorus, carbon (photosynthesis), or stress tolerance metabolism while showing distinct genomic footprints between habitats, e.g., different types of transporters, did not obviously translate into major functionality differences between environments. Brackish microbes show a mixture of marine (salt adaptation pathways) and freshwater features, highlighting their transitional nature. CONCLUSIONS: The plethora of freshwater isolates provided here, in terms of trophic status preference and genetic diversity, exemplifies their ability to colonize ecologically diverse waters across the globe. Moreover, a trend towards larger and more flexible/adaptive genomes in freshwater picocyanobacteria may hint at a wider number of ecological niches in this environment compared to the relatively homogeneous marine system.


Subject(s)
Cyanobacteria , Salinity , Cyanobacteria/genetics , Cyanobacteria/metabolism , Ecosystem , Fresh Water , Proteome/metabolism
7.
Sensors (Basel) ; 23(24)2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38139576

ABSTRACT

This paper introduces the application of a genetic programming (GP)-based method for the automated design and tuning of process controllers, representing a noteworthy advancement in artificial intelligence (AI) within the realm of control engineering. In contrast to already existing work, our GP-based approach operates exclusively in the time domain, incorporating differential operations such as derivatives and integrals without necessitating intermediate inverse Laplace transformations. This unique feature not only simplifies the design process but also ensures the practical implementability of the generated controllers within physical systems. Notably, the GP's functional set extends beyond basic arithmetic operators to include a rich repertoire of mathematical operations, encompassing trigonometric, exponential, and logarithmic functions. This broad set of operations enhances the flexibility and adaptability of the GP-based approach in controller design. To rigorously assess the efficacy of our GP-based approach, we conducted an extensive series of tests to determine its limits and capabilities. In summary, our research establishes the GP-based approach as a promising solution for automating the controller design process, offering a transformative tool to address a spectrum of control problems across various engineering applications.

8.
Molecules ; 28(16)2023 Aug 12.
Article in English | MEDLINE | ID: mdl-37630284

ABSTRACT

The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L = curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry, also confirmed by EPR. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing Crystallinity was additionally assessed by XRD patterns. The log P value of the complex (2.3 ± 0.15) was determined showing the improvement in water solubility. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines, with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

9.
J Youth Adolesc ; 52(2): 406-418, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36396912

ABSTRACT

Bidirectional associations between bullying and cyberbullying have consistently identified during adolescence. However, little is known about how this relationship works on the within-person level, after controlling for potential overlap at the between-person level. This study examined the bidirectional longitudinal associations between bullying and cyberbullying perpetration and victimization during 18-month period over four time points. A total of 2835 participants, aged 11 to 16 years in time 1 (50% girls; Mage = 13.13, SD = 1.06) were surveyed. Random intercept cross-lagged analyses revealed the stability of bullying perpetration and victimization. Cyberbullying victimization predicted inversely bullying and cyberbullying perpetration. The results indicate spirals of positive long-term associations between bullying (perpetration and victimization) and cyberbullying perpetration but no long-terms spirals of victimization.


Subject(s)
Bullying , Crime Victims , Cyberbullying , Adolescent , Female , Humans , Male , Prospective Studies , Interpersonal Relations
10.
Article in English | MEDLINE | ID: mdl-35695851

ABSTRACT

Fourteen strains, all isolated from the surface of freshwater habitats, were genomically, phylogenetically and phenotypically characterized. The strains were obtained from geographically and climatically broadly scattered sites. This included two lakes in Antarctica, one arctic pond located on the Svalbard archipelago (Norway), a tropical habitat located in Uganda, some lakes in Southern Europe (Spain and France), lakes, ponds and a puddle in Central Europe (Austria, Czech Republic and Germany), and lakes in Northern Europe (Finland). Most of the investigated strains were characterized by rather small cell sizes and rather slow growth on media such as nutrient broth-soyotone-yeast extract (NSY) medium. Phylogenomic analyses indicated that all fourteen strains are affiliated with the genus Polynucleobacter (Burkholderiaceae, Pseudomonadota). Thirteen of the strains were found to be affiliated with subcluster PnecC of the genus. All these strains were characterized by genome sizes in the range of 1.7-2.3 Mbp and G+C values of 44.9-46.5 mol%. Furthermore, all PnecC-affiliated strains shared 16S rRNA gene sequence similarities >99 %. Only one strain characterized by a larger genome size of 2.9 Mbp and a lower G+C value of 41.0 mol% was found to be affiliated with subcluster PnecA. Whole genome sequence comparisons revealed that all 14 strains shared among each other, as well as with the type strains of the previously described 17 Polynucleobacter species, whole-genome average nucleotide identities values <95 %. This suggested that the 14 investigated strains represent 14 different new species. We propose the establishment of 14 new Polynucleobacter species represented by the following type strains: UB-Domo-W1T (=DSM 103491T=CIP 111598T=JCM 32562T), VK13T (=DSM 103488T=JCM 32564T), LimPoW16T (=DSM 24085T=CIP 111098T), UK-Long2-W17T (=DSM 103489T=CIP 111328T=JCM 32563T), UK-Pondora-W15T (=DSM 103423T=JCM 32939T), MWH-Mekk-B1T (=DSM 106779T=JCM 32556T), MWH-Mekk-C3T (=DSM 103415T=JCM 32557T), Ross1-W9T (=DSM 103416T=JCM 32561T), MWH-Hall10T (=DSM 107042T=JCM 32938T), AP-Basta-1000A-D1T (=DSM 107039T=JCM 32933T), AP-Melu-1000-A1T (=DSM 107036T=JCM 32935T), es-MAR-2T (=DSM 103424T=JCM 32554T), AP-Mumm-500A-B3T (=DSM 107037T=JCM 32936T), MWH-UH21BT (=DSM 23884T=LMG 29707T).


Subject(s)
Burkholderiaceae , Coleoptera , Animals , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Lakes , MAP Kinase Kinase Kinases/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
11.
Bioorg Chem ; 125: 105924, 2022 08.
Article in English | MEDLINE | ID: mdl-35687940

ABSTRACT

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.


Subject(s)
Antineoplastic Agents , Triterpenes , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Male , Mice , Molecular Docking Simulation , Molecular Structure , Pentacyclic Triterpenes/pharmacology , Pyrazines , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/pharmacology
12.
Bioorg Med Chem Lett ; 38: 127860, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33636301

ABSTRACT

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Artemia/drug effects , Diphenylamine/pharmacology , Edema/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cell Survival/drug effects , Diphenylamine/chemical synthesis , Diphenylamine/chemistry , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/chemically induced , Hydrophobic and Hydrophilic Interactions , Macrophages/drug effects , Mice , Molecular Structure , RAW 264.7 Cells , Structure-Activity Relationship , Tetradecanoylphorbol Acetate/analogs & derivatives
13.
Aggress Behav ; 47(3): 332-342, 2021 05.
Article in English | MEDLINE | ID: mdl-33655507

ABSTRACT

Adolescents' involvement in cyberbullying has been a growing public health concern for some time. Cybervictimization and cyberaggression are two phenomena that previous research has often shown to be associated. However, longitudinal research into these associations and also into potential risk factors for these phenomena is less common. Anger rumination is a proven risk factor for aggressive behavior, but the relationship between anger rumination and victimization is not clear. The present longitudinal study investigated the associations between cybervictimization, anger rumination and cyberbullying in a sample of 3017 adolescents (MW1 = 13.15; SD = 1.09; 49% girls) from 7th to 9th grade. The European Cyberbullying Intervention Project Questionnaire and the Anger Rumination Scale were administered in four waves with 6 months intervals over a total period of 18 months. The associations between the variables were analyzed with a cross-lagged model. We found that: cybervictimization predicted anger rumination and cyberaggression; anger rumination was associated with later increases in both cybervictimization and cyberaggression: but involvement in cyberaggression predicted neither subsequent involvement in cybervictimization, nor in anger rumination. In addition, cybervictimization was found to mediate the association between anger rumination and cyberaggression. This study expands the understanding of the factors associated with cybervictimization and cyberaggression, and its results indicate that intervention programs should focus on boosting self-control to decrease impulsive behavior and protocols to prevent and intervene in cyberbullying.


Subject(s)
Bullying , Crime Victims , Cyberbullying , Adolescent , Anger , Female , Humans , Longitudinal Studies
14.
J Youth Adolesc ; 50(10): 2021-2035, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34331660

ABSTRACT

Precursors and consequences of bullying have been widely explored, but much remains unclear about the association of moral and motivational factors. This study examined longitudinal associations between need for popularity, moral disengagement, and bullying perpetration. A total of 3017 participants, aged 11 to 16 years in wave 1 (49% girls; Mage = 13.15, SD = 1.09), were surveyed across four waves with six-month intervals. At the between-person level, cross-lagged modeling revealed a positive bidirectional association between moral disengagement and need for popularity; bullying perpetration was predicted by both need for popularity and moral disengagement. From the within-person level, random intercept cross-lagged analyses revealed that need for popularity predicted both moral disengagement and bullying perpetration. The results highlight the interplay between motivational and moral mechanisms that underlies bullying behavior.


Subject(s)
Adolescent Behavior , Bullying , Adolescent , Female , Humans , Male , Morals , Surveys and Questionnaires
15.
Bioorg Chem ; 100: 103919, 2020 07.
Article in English | MEDLINE | ID: mdl-32417524

ABSTRACT

Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3ß-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3ß-hydroxy-hop-22(29)-ene (3). ß-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties.


Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Euphorbiaceae/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Male , Mice , Molecular Docking Simulation , Triterpenes/isolation & purification , Yeasts/enzymology , alpha-Glucosidases/metabolism
16.
J Clin Lab Anal ; 34(5): e23209, 2020 May.
Article in English | MEDLINE | ID: mdl-31978276

ABSTRACT

BACKGROUND: Functional variants -173 G > C (rs755622) and -794CATT5-8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico. MATERIALS AND METHODS: A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes -173 G > C and -794 CATT5-8 MIF polymorphisms was performed by PCR-RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively. RESULTS: The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants -173G > C and -794 CATT5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found. CONCLUSION: The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles -173*C and -794CATT7 are associated with the increase of MIF circulating in women with BC.


Subject(s)
Breast Neoplasms/genetics , Intramolecular Oxidoreductases/blood , Intramolecular Oxidoreductases/genetics , Macrophage Migration-Inhibitory Factors/blood , Macrophage Migration-Inhibitory Factors/genetics , Tumor Necrosis Factor-alpha/blood , Adult , Breast Neoplasms/blood , Case-Control Studies , Cross-Sectional Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Mexico , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Solubility , Tumor Necrosis Factor-alpha/genetics
17.
Phytochem Anal ; 31(2): 252-261, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31433543

ABSTRACT

INTRODUCTION: Previous studies report the isolation mainly of terthiophene derivatives and flavonoids from Dyssodia species. Terthiophenes are known as photosensitizers by their capacity to generate singlet oxygen (1 O2 ), and flavonoid antioxidant activity is recognized. These opposite properties could represent interesting options in photodynamic therapy. OBJECTIVE: To determine the antioxidant and photosensitizer activities of extracts and isolates of Dyssodia pinnata by electron paramagnetic resonance (EPR). METHODOLOGY: Extracts and isolates were evaluated as antioxidants by the interactions with copper ion (Cu2+ ) observed in EPR, and by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and the thiobarbituric reactive substances (TBARS) methods. Their abilities as 1 O2 producers were also estimated by EPR. RESULTS: Terthiophenes were obtained from hexane (DPH) and acetone (DPA) extracts, and flavonoids from DPA and methanol (DPM) extracts. The interaction with Cu2+ of extracts and isolated compounds of Dyssodia pinnata showed two effects in EPR: reduction and chelation; flavonoids exhibited both effects, while terthiophenes showed only reduction. DPA, DPM, and flavonoids were active in DPPH and TBARS assays. Quercetagetin-7-O-ß-glucoside showed the highest antioxidant and chelating activities, 3-glycosidated flavonoids were less active. Upon irradiation extracts and terthiophenes induced 1 O2 formation. CONCLUSION: Flavonoid reducing activity on Cu2+ and free radical scavenging capacity were related to the number of hydroxy groups and to the conjugation between the B and C rings. All tested flavonols showed a major complex with Cu2+ , with the most probable site of chelation between the 5-hydroxy and 4-oxo groups. Extracts and terthiophene derivatives showed photosensitizer activity. Thus, EPR is useful to evaluate free radical scavenging and pro-oxidant properties.


Subject(s)
Antioxidants , Photosensitizing Agents , Electron Spin Resonance Spectroscopy , Flavonoids , Free Radical Scavengers , Phenols , Plant Extracts
18.
Int J Mol Sci ; 21(15)2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32752280

ABSTRACT

Goat's milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat's milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat's milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat's milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.


Subject(s)
Energy Metabolism/drug effects , Fatty Acids/administration & dosage , Fatty Liver/prevention & control , Milk/chemistry , Mitochondria, Muscle/drug effects , Muscle, Skeletal/drug effects , Obesity/prevention & control , Animals , Biomarkers/analysis , Diet, High-Fat/adverse effects , Dietary Supplements , Fatty Liver/etiology , Gene Expression/drug effects , Goats , Insulin Resistance , Linoleic Acids, Conjugated/administration & dosage , Male , Mice, Inbred C57BL , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Obesity/etiology
19.
Molecules ; 25(8)2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32326502

ABSTRACT

The aerial parts of Salvia cinnabarina afforded two undescribed labdane diterpenoids 1 and 2 (malonylcommunol and 6ß-hydroxy-trans-communic acid) along with two known labdane diterpenoids, trans-communic acid (3) and trans-communol (4). Additionally, seven known metabolites were also isolated; two isopimarane diterpenoids 5 and 6, two sesquiterpenoids identified as ß-eudesmol (7) and cryptomeridiol (8), and three aromatic compounds identified as phthalic acid (9), a mixture of tyrosol fatty acid esters (10) and the flavone salvigenine (11). While compounds compounds 1-3 showed significant inhibition of yeast α-glucosidase, compounds 2, 3 and 7 had no anti-inflammatory activity in the edema model induced by TPA. This paper is not only the first report on a wild population of Salvia cinnabarina, but also of the presence of labdane-type diterpenoids in a Mexican Salvia sp.


Subject(s)
Diterpenes/chemistry , Models, Molecular , Molecular Structure , Salvia/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Dose-Response Relationship, Drug , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Magnetic Resonance Spectroscopy , Structure-Activity Relationship
20.
Molecules ; 25(5)2020 Feb 26.
Article in English | MEDLINE | ID: mdl-32110921

ABSTRACT

Lectins are bioactive proteins with the ability to recognize cell membrane carbohydrates in a specific way. Diverse plant lectins have shown diagnostic and therapeutic potential against cancer, and their cytotoxicity against transformed cells is mediated through the induction of apoptosis. Previous works have determined the cytotoxic activity of a Tepary bean (Phaseolus acutifolius) lectin fraction (TBLF) and its anti-tumorigenic effect on colon cancer. In this work, lectins from the TBLF were additionally purified by ionic-exchange chromatography. Two peaks with agglutination activity were obtained: one of them was named TBL-IE2 and showed a single protein band in two-dimensional electrophoresis; this one was thus selected for coupling to quantum dot (QD) nanoparticles by microfluidics (TBL-IE2-QD). The microfluidic method led to low sample usage, and resulted in homogeneous complexes, whose visualization was achieved using multiphoton and transmission electron microscopy. The average particle size (380 nm) and the average zeta potential (-18.51 mV) were determined. The cytotoxicity of the TBL-IE2 and TBL-IE2-QD was assayed on HT-29 colon cancer cells, showing no differences between them (p ≤ 0.05), where the LC50 values were 1.0 × 10-3 and 1.7 × 10-3 mg/mL, respectively. The microfluidic technique allowed control of the coupling between the QD and the protein, substantially improving the labelling process, providing a rapid and efficient method that enabled the traceability of lectins. Future studies will focus on the potential use of the QD-labelled lectin to recognize tumor tissues.


Subject(s)
Microfluidics , Phaseolus/metabolism , Plant Lectins/metabolism , Quantum Dots/metabolism , Staining and Labeling , Cell Death/drug effects , Fluorescence , HT29 Cells , Humans , Plant Lectins/isolation & purification , Plant Lectins/pharmacology
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