Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA

Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobility Metabolomic Mass Spectrometry platform, combined with the analysis of a panel of circulating microRNAs (miR). By coupling CIMS ion mobility technology with SANIST, we were able to reveal three new structures among the most differentially expressed metabolites in PCa vs. BPH. In particular, two were classified as polyunsaturated ceramide ester-like and one as polysaturated glycerol ester-like. Penalized logistic regression was applied to build a model to predict PCa, using six circulating miR, seven circulating metabolites, and demographic/clinical variables, as covariates. Four circulating metabolites, miR-5100, and age were selected by the model, and the corresponding prediction score gave an AUC of 0.76 (C.I. = 0.66–0.85). At a specified cut-off, no high-risk tumor was misclassified, and 22 out of 53 BPH were correctly identified, reducing by 40% the false positives of PSA. We developed and applied a novel, minimally invasive, liquid biopsy-based powerful tool to characterize novel metabolites and identified new potential non-invasive biomarkers to better predict PCa, when PSA is uninformative as a tool for precision medicine in genitourinary cancers.

Re-charging your fats: Charmm36 parameters for neutral lipids triacylglycerol and diacylglycerol

Neutral lipids (NLs) are an abundant class of cellular lipids. They are characterized by the total lack of charged chemical groups in their structure, and, as a consequence, they play a major role in intracellular lipid storage. NLs that carry a glycerol backbone, such as triacylglycerols (TGs) and diacylglycerols (DGs), are also involved in the biosynthetic pathway of cellular phospholipids, and they have recently been the subject of numerous structural investigations by means of atomistic molecular dynamics (MD) simulations. However, conflicting results on the physicochemical behavior of NLs were observed depending on the nature of the atomistic force field used. Here, we show that current phospholipid-derived CHARMM36 parameters for DGs and TGs cannot reproduce adequately interfacial properties of these NLs, due to excessive hydrophilicity at the glycerol-ester region. By following a CHARMM36-consistent parameterization strategy, we develop new parameters for both TGs and DGs that are compatible with both cutoff- based and Particle Mesh Ewald (PME) schemes for the treatment of Lennard Jones interactions. We show that our new parameters can reproduce interfacial properties of NLs and their behavior in more complex lipid assemblies. We discuss the implications of our findings in the context of intracellular lipid storage and NLs cellular activity.

Combustion behaviors of hydrogenated and unhydrogenated colophony esters/petroleum resins using TG-FTIR and DFT analysis

The combustion behavior of tackifying resins (such as glycerol ester of colophony/hydrogenated colophony and C9/hydrogenated C9 petroleum resin, namely GEC, GEHC, C9PR and HC9PR, respectively) were investigated using TG-FTIR and density functional theory (DFT) analyses. Results from combustion characteristics indicate tackifying resins and their wastes are a promising fuel for generating energy. The average activation energies obtained by Friedman method for GEC, GEHC, C9PR and HC9PR were 223.51, 162.16, 166.52 and 116.20 kJ/mol, respectively, revealing that (H)C9PR were more readily combustible than GE(H)C, and their hydrogenated products burned more easily than their unhydrogenated ones, which were strongly supported by the TG-FTIR results. DFT calculations also show that the bond dissociation energy of C-C bond of GEC is higher than those of C9PR and GEHC. The best appropriate reaction mechanism evaluated by integral master plots is f(α)=3(1-α)2/3. Volatiles are mainly composed of H2O, CH4, CO2, CO, alcohol, aromatic and carbonyl compounds.

The role of pumpkin pulp extract carotenoids against mycotoxin damage in the blood brain barrier in vitro

Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.

Films Based on Thermoplastic Starch Blended with Pine Resin Derivatives for Food Packaging

Completely biobased and biodegradable thermoplastic starch (TPS) based materials with a tunable performance were prepared for food packaging applications. Five blends were prepared by blending TPS with 10 wt%. of different pine resins derivatives: gum rosin (GR), disproportionated gum rosin (RD), maleic anhydride-modified gum rosin (CM), pentaerythritol ester of gum rosin (LF), and glycerol ester of gum rosin (UG). The materials were characterized in terms of thermo-mechanical behavior, surface wettability, color performance, water absorption, X-ray diffraction pattern, and disintegration under composting conditions. It was determined that pine resin derivatives increase the hydrophobicity of TPS and also increase the elastic component of TPS which stiffen the TPS structure. The water uptake study revealed that GR and LF were able to decrease the water absorption of TPS, while the rest of the resins kept the water uptake ability. X-ray diffraction analyses revealed that GR, CM, and RD restrain the aging of TPS after 24 months of aging. Finally, all TPS-resin blends were disintegrated under composting conditions during the thermophilic incubation period (90 days). Because of the TPS-resin blend’s performance, the prepared materials are suitable for biodegradable rigid food packaging applications.

Metabolic effects of agro-infiltration on N. benthamiana accessions

Over the recent years, Nicotiana benthamiana has gained great importance as a chassis for the production of high value, low volume pharmaceuticals and/or active pharmaceutical ingredients (APIs). The process involving infiltration of the N. benthamiana leaves with Agrobacterium spp, harbouring vectors with the gene of interest, facilitates transient expression. To date, little information is available on the effect of the agro-infiltration process on the metabolome of N. benthamiana, which is necessary to improve the process for large-scale, renewable manufacturing of high value compounds and medical products. Hence, the objective of the present study was to assess metabolic adaptation of N. benthamiana as a response to the presence of Agrobacterium. The present study elucidated changes of the steady-state metabolism in the agroinfiltrated leaf area, the area around the infection and the rest of the plant. Furthermore, the study discusses the phenotypic advantages of the N. benthamiana lab strain, optimised for agro-infiltration, compared to three other wild accessions. Results showed that the lab strain has a different metabolic composition and showed less alterations of the phenylpropanoid pathway and cell wall remodelling in the agroinfiltrated leaf areas, for example chlorogenic acid, cadaverine and C18:0–2-glycerol ester. In conclusion, both of these alterations present potential candidates to improve the phenotype of the N. benthamiana lab strain for a more efficient transient expression process.

PERBEDAAN KADAR GLISEROL, ESTER, MONO- DAN DIGLISERIDA PADA VARIASI PERLAKUAN REFINED BLEACHED DEODORIZED PALM OIL

Refined Bleached Deodorized Palm Oil (RBDPO) is a derived product of crude palm oil that has two fraction (olein and stearin) in ambient temperature. This research aim to analyze the variation of treatment on RBDPO. The design of research was non-factorial with three variable of treatment such RBDPO with glycerol (A), RBDPO (B) and RBDPO with lipase enzyme. The concentration of glycerol, ester, mono- and diglyceride was tested by Gas Chromatography method. The data will be analyzed by using descriptive method with boxplot and histogram. The result showed that the highest concentration of glycerol; ester; mono- and diglyceride respectively were showed in treatment B (1,5922%); C (9,5699%); C (0,1783%); C (3,3329). The boxplot graphic described the differences among the treatment.

Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides

Branched esters of palmitic acid and hydroxy stearic acid are antiinflammatory and antidiabetic lipokines that belong to a family of fatty acid (FA) esters of hydroxy fatty acids (HFAs) called FAHFAs. FAHFAs themselves belong to oligomeric FA esters, known as estolides. Glycerol-bound FAHFAs in triacylglycerols (TAGs), named TAG estolides, serve as metabolite reservoir of FAHFAs mobilized by lipases upon demand. Here, we characterized the involvement of two major metabolic lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in TAG estolide and FAHFA degradation. We synthesized a library of 20 TAG estolide isomers with FAHFAs varying in branching position, chain length, saturation grade, and position on the glycerol backbone and developed an in silico mass spectra library of all predicted catabolic intermediates. We found that ATGL alone or coactivated by comparative gene identification-58 efficiently liberated FAHFAs from TAG estolides with a preference for more compact substrates where the estolide branching point is located near the glycerol ester bond. ATGL was further involved in transesterification and remodeling reactions leading to the formation of TAG estolides with alternative acyl compositions. HSL represented a much more potent estolide bond hydrolase for both TAG estolides and free FAHFAs. FAHFA and TAG estolide accumulation in white adipose tissue of mice lacking HSL argued for a functional role of HSL in estolide catabolism in vivo. Our data show that ATGL and HSL participate in the metabolism of estolides and TAG estolides in distinct manners and are likely to affect the lipokine function of FAHFAs.

Chemoenzymatic Synthesis of the New 3-((2,3-Diacetoxypropanoyl)oxy)propane-1,2-diyl Diacetate Using Immobilized Lipase B from Candida antarctica and Pyridinium Chlorochromate as an Oxidizing Agent

To exploit the hydrolytic activity and high selectivity of immobilized lipase B from Candida antarctica on octyl agarose (CALB-OC) in the hydrolysis of triacetin and also to produce new value-added compounds from glycerol, this work describes a chemoenzymatic methodology for the synthesis of the new dimeric glycerol ester 3-((2,3-diacetoxypropanoyl)oxy)propane-1,2-diyl diacetate. According to this approach, triacetin was regioselectively hydrolyzed to 1,2-diacetin with CALB-OC. The diglyceride product was subsequently oxidized with pyridinium chlorochromate (PCC) and a dimeric ester was isolated as the only product. It was found that the medium acidity during the PCC treatment and a high 1,2-diacetin concentration favored the formation of the ester. The synthesized compounds were characterized using IR, MS, HR-MS, and NMR techniques. The obtained dimeric ester was evaluated at 100 ppm against seven bacterial strains and two Candida species to identify its antimicrobial activity. The compound has no inhibitory activity against the bacterial strains used but decreased C. albicans and C. parapsilosis growth by 49% and 68%, respectively. Hemolytic activity was evaluated, and the results obtained support the use of the dimeric ester to control C. albicans and C. parapsilosis growth in non-intravenous applications because the compound shows hemolytic activity.

Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening

Flavor and spice is largely consumed in food, cosmetics, and pharmaceutical industries. A novel coronavirus, recently named the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was first identified in humans in Wuhan China in 2019. This study is to examine whether the flavor components can prevent human from SARS-CoV-2 infection. Given that the druggable antiviral target ACE2 receptor and viral main protease were reported, 169 compounds were screened against these two targets by using autodock vina. According to our docking screening, 10 antiviral components, including glycyrrhizic acid, theaflavin 3,3'-digallate, agnuside, fenflumizole, angelicide, sageone, oleanic acid, benzyl (3-fluoro-4-morpholine-4-yl phenyl) carbamate, glycerol ester of rosin, and endere S can directly bind to both host cell target ACE2 receptor and viral target main protease, indicating their potential for SARS-CoV-2 treatment.