Antioxidant and antibacterial properties of ethanolic pot-pollen extract of Melipona beecheii and determination of the major components by GC-MS.

Melipona beecheii pot-pollen is a natural product that has barely been studied, unlike other hive products such as honey and propolis. Its application has been reported since ancient times in traditional Mayan medicine, and it is also a functional food with high nutritional value. In the present study, samples of ethanolic pot-pollen extracts from five locations in the Yucatán Peninsula were analyzed to determine their antibacterial and antioxidant properties. All the extracts showed activity against five medically important bacteria; Pseudomonas aeruginosa and Listeria monocytogenes were the most susceptible bacteria in all samples. The evaluated antioxidant activity was higher than that reported by other studies. Palmitic, linoleic, and linolenic fatty acids and their respective ethyl ethers were detected by Gas Chromatography-Mass Spectrometry (GC-MS) in all samples in different concentrations. Based on these results, pot-pollen extract from Mama, Yucatán exhibited the best biological activities (Minimum Inhibitory Concentrations (MICs) between 6 and 40 mg/mL, EC50 DPPH 28 µg/mL, EC50 RP 30 µg/mL), which could be related to a higher content of unsaturated fatty acids and their ethyl esters. The present study demonstrates that M. beecheii pot-pollen has therapeutic potential in addition to its benefits as a nutritional supplement.

Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans.

Lomentospora prolificans is a pathogenic and multidrug-resistant fungus that can infect both immunocompetent and immunocompromised patients, with mortality rates up to 87%. The World Health Organization (WHO) included this fungal species in its first list of 19 priority fungal pathogens, which focused on fungal pathogens that can cause invasive acute and subacute systemic fungal infections. Therefore, there is a growing interest in finding new therapeutic alternatives. In this work, the synthesis of twelve α-aminophosphonates by the microwave-assisted Kabachnik-Fields reaction and twelve α-aminophosphonic acids by a monohydrolysis reaction is reported. All compounds were evaluated by the agar diffusion method as a preliminary screening in comparison with voriconazole, showing inhibition halos for compounds 7, 11, 13, 22 and 27. The five active compounds in the preliminary tests were evaluated against five strains of L. prolificans following protocol M38-A2 from CLSI. The results showed that these compounds exhibit antifungal activity in the concentration range of 900->900 µg/mL. Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay, and it was shown that compound 22 was the least cytotoxic, with a viability of 67.91%, comparable to the viability exhibited by voriconazole (68.55%). Docking studies showed that the possible mechanism of action of the active compounds could be through the inhibition of the enzyme lanosterol-14-alpha-demethylase in an allosteric hydrophobic cavity.

Preparation and Characterization of Strongly Sulfonated Acid Block and Random Copolymer Membranes for Acetic Acid Esterification with 2-Propanol.

In this paper, we report the synthesis of block and random copolymers of 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) and methyl methacrylate (MMA), with different AMPS feed ratios. These solution-processable copolymers with strongly sulfonated acid groups resulted in membranes with tunable ion exchange (IEC) and water absorption capacities. AFM images confirmed the microphase separation of PAMPS-b-PMMA-1:1 block copolymer membrane, annealed under the appropriate conditions. The resulting copolymers from the random combination of a 1:1 molar ratio of AMPS and MMA monomers are effective at enhancing the esterification conversion of acetic acid, when compared with a reaction catalyzed by PAMPS-b-PMMA block copolymers and the previously studied catalytic membranes. With the PAMPS-co-PMMA-1:1 membrane, the esterification reaction using acetic acid achieved 85% isopropyl acetate. These results are closely correlated with the increase in IEC (2.63 mmol H+g-1) and the relationship between weight loss (20.3%) and swelling degree (68%) in 2-propanol.

Assessing the Effect of Chemical Dispersant Nokomis 3-F4 on the Degradation of a Heavy Crude Oil in Water by a Marine Microbial Consortium.

Degradation efficiency of a heavy crude oil by a marine microbial consortium was evaluated in this study, with and without the addition of a chemical dispersant (Nokomis 3-F4). 15.50% of total petroleum hydrocarbons (TPH) were removed after 15 days of incubation without dispersant, with a degradation rate of 2.39 ± 0.22 mg L-1 day-1. In contrast, the addition of Nokomis 3-F4 increased TPH degradation up to 30.81% with a degradation rate of 5.07 ± 0.37 mg L-1 day-1. 16S rRNA gene sequencing indicated a dominance of the consortium by Achromobacter and Alcanivorax. Nonetheless, significant increases in the relative abundance of Martelella and Ochrobactrum were observed with the addition of Nokomis 3-F4. These results will contribute to further environmental studies of the Gulf of Mexico, where Nokomis 3-F4 can be used as chemical dispersant.

Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect.

Substituted phenylacetic (1-3), phenylpropanoic (4-6), and benzylidenethiazolidine-2,4-dione (7-9) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements. Addition and substitution reactions were performed to obtain molecules at moderated yields. In silico pharmacological consensus analysis (PHACA) was conducted to determine their possible modes of action, protein affinities, toxicological activities, and drug-like properties. The results were combined with in vivo assays to evaluate the ability of these compounds to decrease glucose levels in diabetic mice at a 100 mg/kg single dose. Compounds 6 (a phenylpropanoic acid derivative) and 9 (a benzylidenethiazolidine-2,4-dione derivative) ameliorated the hyperglycemic peak in a statically significant manner in a mouse model of type 2 diabetes. Finally, molecular dynamics simulations were executed on the top performing compounds to shed light on their mechanism of action. The simulations showed the flexible nature of the binding pocket of AR, and showed that both compounds remained bound during the simulation time, although not sharing the same binding mode. In conclusion, we designed nine acid bioisosteres with robust in vivo antihyperglycemic activity that were predicted to have favorable pharmacokinetic and toxicological profiles. Together, these findings provide evidence that supports the molecular design we employed, where the unified pharmacophores possess a strong antidiabetic action due to their multitarget activation.

Alterations in the Gut Microbiota of Zebrafish (Danio rerio) in Response to Water-Soluble Crude Oil Components and Its Mixture With a Chemical Dispersant.

Crude oil spills have caused substantial impacts to aquatic ecosystems. Chemical dispersants are used to palliate the impact of oil spillages, but their use is polemic due to their additional potential toxic effect when mixed with oil-derived components. In this work, we used a 16S-based metagenomic approach to analyze the changes of the gut microbiota of adult zebrafish (Danio rerio) exposed to the water accommodated fraction (WAF) of a light crude oil (35° API gravity), and the chemically enhanced WAF (CEWAF), prepared with Nokomis 3-F4® dispersant. After 96 h of exposure, WAF induced an increase in the alpha and beta diversity, altering the relative abundance of Vibrio, Flavobacterium, and Novosphingobium. In contrast, CEWAF only caused an increase in the beta diversity, and an enrichment of the genus Pseudomona. Both treatments diminished the abundances of Aeromonas, Cetobacterium, Coxiella, Dinghuibacter, and Paucibacter. Moreover, the co-occurrence network among genera was more complex in WAF than in CEWAF, indicating a greater bacterial interaction in response to WAF. Our results indicate that short-term exposure to WAF and CEWAF can induce a dysbiosis in the gut microbiota of D. rerio, but these changes are specific in each treatment.

1H NMR metabolomic analysis of skin and blubber of bottlenose dolphins reveals a functional metabolic dichotomy.

The common bottlenose dolphin (Tursiops truncatus) is a carnivorous cetacean that thrives in marine environments, one of the apex predators of the marine food web. They are found in coastal and estuarine ecosystems, which are known to be sensitive to environmental impacts. Dolphins are considered sentinel organisms for monitoring the health of coastal marine ecosystems due to their role as predators that can bioaccumulate contaminants. Although recent studies have focused on capturing the circulating metabolomes of these mammals, and in the context of pollutants and exposures in the marine environment, skin and blubber are important surface and protective tissues that have not been adequately probed for metabolism. Using a proton nuclear magnetic resonance spectroscopy (1H NMR) based metabolomics approach, we quantified 51 metabolites belonging to 74 different metabolic pathways in the skin and blubber of stranded bottlenose dolphin (n = 4) samples collected at different localities in the Southern Zone coast of Yucatan Peninsula of Mexico. Results indicate that metabolism of skin and blubber are quantitatively very different. These metabolite abundances could help discriminate the tissue-types using supervised partial least square regression discriminant analysis (PLSDA). Further, using hierarchical clustering analysis and random forest analysis of the metabolite abundances, the results pointed to unique metabolites that are important classifiers of the tissue-type. On one hand, the differential metabolic patterns, mainly linking fatty acid metabolism and ketogenic amino acids, seem to constitute a characteristic of blubber, thus pointing to fat synthesis and deposition. On the other hand, the skin showed several metabolites involved in gluconeogenic pathways, pointing towards an active anabolic energy-generating metabolism. The most notable pathways found in both tissues included: urea cycle, nucleotide metabolism, amino acid metabolism, glutathione metabolism among others. Our 1H NMR metabolomics analysis allowed the quantification of metabolites associated with these two organs, i.e., pyruvic acid, arginine, ornithine, 2-hydroxybutyric acid, 3-hydroxyisobutyric acid, and acetic acid, as discriminatory and classifying metabolites. These results would lead to further understanding of the functional and physiological roles of dolphin skin and blubber metabolism for better efforts in their conservation, as well as useful target biopsy tissues for monitoring of dolphin health conditions in marine pollution and ecotoxicology studies.

Gene expression profile and molecular pathway datasets resulting from benzo(a)pyrene exposure in the liver and testis of adult tilapia.

Benzo(a)pyrene (BaP), the prototype of polycyclic aromatic hydrocarbons, is known to exhibits genotoxic and carcinogenic effects promoting molecular impacts. The dataset presented here is associated with the research article paper entitled "Transcriptome Analysis Reveals Novel Insights Into the Response of Low-dose Benzo(a)pyrene Exposure in Male Tilapia". In this article, we presented a transcriptomic characterization of male tilapia exposure to BaP in the short term. This data provides an extended analysis of changes in the gene expression and identification of pathways in the liver and testis of male tilapia exposure to BaP. We used gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) to identify gene networks and pathways associated with molecular adverse effects of BaP exposure. The data indicates that target pathways related to promoting carcinogenesis such as DNA repair and DNA replication were affected as well as other crucial biological processes. Moreover, to determine whether some of the key reported genes of DNA damage are affected by BaP exposure, Quantitative PCR (qPCR) was performed. Gene set categories and sub-networks are provided and the corresponding signature differences from BaP exposure are listed. The information in these datasets may contribute to understanding the potential carcinogenesis mechanism of action from low BaP exposure.

Transcriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapia.

Despite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption. We used both high-throughput RNA-Sequencing to assess whole genome gene expression following repeated intraperitoneal injections of 3 mg/kg of BaP (every 6 days for 26 days) and morphometric endpoints as indicators of general health. Condition factor (K) along with hepatosomatic and gonadosomatic indices (morphometric parameters) were significantly lower in BaP-treated fish than in controls. BaP exposure induced important changes in the gene expression pattern in liver and testis as revealed by both Pathway and Gene Ontology (GO) analyses. Alterations that were shared by both tissues included arachidonic acid metabolism, androgen receptor to prostate-specific antigen signaling, and insulin-associated effects on lipogenesis. The most salient liver-specific effects included: biological processes involved in detoxification, IL6-associated insulin resistance, mTOR hyperactivation, mitotic cytokinesis, spindle pole and microtubule binding. BaP effects that were confined to the testis included: immune system functions, inflammatory response, estrogen and androgen metabolic pathways. Taken together, gene expression and morphometric end point data indicate that the reproductive success of adult male tilapia could be compromised as a result of BaP exposure. These results constitute new insights on the mechanism of action of low dose BaP in a non-model organism (tilapia).

Design, Synthesis and in Combo Antidiabetic Bioevaluation of Multitarget Phenylpropanoic Acids.

We have synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids employing an easy and short synthetic pathway. The compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: G protein-coupled receptor 40 (GPR40), aldose reductase (AKR1B1), peroxisome proliferator-activated receptor gama (PPARγ) and solute carrier family 2 (facilitated glucose transporter), member 4 (GLUT-4). Compound 1 displayed an EC50 value of 0.075 µM against GPR40 and was an AKR1B1 inhibitor, showing IC50 = 7.4 µM. Compounds 2 and 3 act as slightly AKR1B1 inhibitors, potent GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active molecules on these targets, showing several coincidences with co-crystal ligands. Compounds 1-3 were tested in vivo at an explorative 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non-insulin-dependent diabetes mice model. Compounds 2 and 3 displayed robust in vitro potency and in vivo efficacy, and could be considered as promising multitarget antidiabetic candidates. This is the first report of a single molecule with these four polypharmacological target action.