Skatole Research Articles

Enhanced HPLC Method for Boar Taint Quantification.

Boar taint is an unpleasant odour found in the carcasses of entire male pigs, resulting from androstenone and skatole accumulation during pubertal development, and impacting pork quality. This study proposes the validation of an adapted chromatographic method for quantifying skatole and androstenone in the pigs' liquid fat using fluorescence detection. A good chromatographic separation was achieved, with skatole (SKA) and androstenone (AND) elution at 4.4 and 9.9 min., respectively. An external calibration method was applied, with calibration curves correlation coefficient of 0.9999 for both analytes. Detection limit values were 1.53 and 16.02 ng/g for SKA and AND, respectively. SKA recovery was 99.72±2.34 % (2.34 % RSD) and 102.84±1.62 % (1.57 % RSD) for AND. Results showed good precision values (repeatability <2.46 % RSD for SKA, <6.85 % RSD for AND; intermediate precision <2.87 % RSD for SKA, <6.98 % RSD for AND). The method's robustness was tested and the values were within the reference ranges. The validation results proved that the adaptation of an existing method resulted in good assessments of robustness, reliability and accuracy.

Palladium nanoparticle catalyzed synthesis of indoles via intramolecular Heck cyclisation.

A system utilizing palladium(II)-PEG has been devised for the intramolecular Heck cyclization of N-vinyl and N-allyl-2-haloanilines. The synthesis of a variety of indoles, including 2,3-diester substituted ones and 3-methyl indoles, has been accomplished using this catalytic system. The N-vinyl starting materials are obtained by the aza-Michael addition of 2-haloanilines with alkynecarboxylate esters, which, upon cyclization, yield ester-substituted indoles. Conversely, N-allyl-2-haloanilines yield 3-methylated indoles as the major products. The high activity of the system is owed to the in situ generation of Pd nanoparticles.

Development of a photoenzymatic one-pot hybrid system for the direct synthesis of 3,3-disubstituted indole-2-ketones from N-methyl indoles

The effective combination of photocatalysis and enzyme catalysis has been widely utilized for the synthesis of high-value-added products.

Gut Microbiota Ecological and Functional Modulation in Post-Stroke Recovery Patients: An Italian Study.

Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as Bacteroides, Christensellaceae, Alistipes and Akkermansia. Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of Akkermansia and enrichment of acetic acid could be considered potential disease phenotype signatures.

PSVI-5 Optimizing Limited Deep Phenotyping Capacity for Genetic Studies and Routine Genetic Evaluations: Application to Boar Taint

Abstract In the context of genetic research, but even more for routine genetic evaluations, a recurrent problem is the difficulty to obtain measurements for certain required phenotypes. This can be caused by limited facilities, difficulties in sampling, expensive analyses, limited staff relative to number of animals, and many other reasons. It may therefore be necessary to select which animals to phenotype while maintaining the phenotyping quality and avoiding bias or omitting some animals of interest. This implies developing strategies to do the phenotyping in a non-biased way using a priori available minimum knowledge. An example could be predicting post weaning growth of cattle based on earlier information as birth weight and weaning weight to optimize the use of feed intake or methane measurement facilities. In pigs, similar situations might occur for growth or emissions. However, another important example is boar taint (BT) which shows that not only sequential weighing, but also partial measurements of BT may require attention. BT is defined as urinary and fecal and associated with 2 major compounds, androstenone (AND) and skatole (SKA). The classical method of odor discrimination, “Human Nose Score” (HNS), is notoriously unreliable. Even if odor is known to be complex, adding AND and SKA to HNS would help reveal better the boar taint condition (i.e., phenotype). However, the measurements of AND and SKA or other compounds in fat are expensive. Therefore, it would be important to optimize these measurements by selecting relevant fat samples taken at slaughterhouses. We tested the following optimization strategy. The objective was to obtain a good distribution of a posteriori measured AND and SKA in the selected samples given initial asymmetric populations with positive HNS (3 to 10% declared positives). In a first step, the strategy pooled 2 available HNS for 997 across 22 contemporary groups (CG) and added limited chemical measurements (218/997) available for older samples. The data were obtained from a boar progeny testing scheme; therefore, CG were linked through connecting sires from artificial insemination having sons in different CG. A multi-trait BLUP model was used adjusting for metabolic weight using a 4-generation pedigree. A total of 15% of the animals in the last 6 contemporary groups were selected using first positive HNS (17/300), then keeping the highest and lowest predictions and maintaining diversity by not repeating boars from the same sire-family (i.e., when a family was already present, the next animal was taken). A posteriori chemical analyses were performed on selected samples to compare predicted and observed classifications in tainted and untainted. Research showed an accuracy of 0.73 (Table 1), leading to 58% tainted and 42% untainted compared with the expected ratio. Improvements of this strategy are currently in development, including using genomics.

Melatonin disturbed rumen microflora structure and metabolic pathways in vitro.

Melatonin (MLT) can affect the microbial community structure and its metabolites by releasing cellular regulatory factors. Intestinal bacteria recognize and respond to MLT signals from the intestine through MLT binding sites and further activate the function of intestinal immune cells. However, the signal transduction pathway of MLT in the intestine has not been clearly elucidated yet. The effect of MLT on rumen bacterial metabolism was studied by simulating rumen fermentation in vitro. The test was divided into three groups: artificial saliva+standard MLT solution (CK0 group), artificial saliva+rumen juice (CK1 group), and artificial saliva+rumen juice+standard MLT solution (MLT group). The fermentation broth was collected after 24 h of simulated culture in vitro. The results showed that the addition of MLT significantly increased the contents of propionic acid, butyric acid, valeric acid, and total volatile fatty acids (P < 0.05). The analysis of the differences in flora found that at the genus level, Alistipes, Veillonellaceae_UCG-001, Selenomonas, Lachnospiraceae_NK4A136_group, and Succinivibrio were significantly increased, whereas Acinetobacter and Prevotella were significantly decreased (P < 0.05). The analysis of differential metabolites showed that compared with the CK1 group, the relative contents of glutathione, spermidine, indole, 3-methyl indole, phenylpyruvate, and other metabolites were increased significantly in the MLT group (P < 0.05). The results of enzyme activity on the enrichment pathway showed that MLT could significantly enhance the activities of genes such as GST, SPDS, DAHP, AS, TS, TPH, AANAT, ASMT, and IDO. Therefore, melatonin had certain regulatory effects on rumen microorganisms and their metabolic pathways.IMPORTANCEIn in vitro studies, it has been found that the effects of MLT on rumen microorganisms and metabolites can change the rumen flora structure, significantly inhibit the relative abundance of harmful Acinetobacter, and improve the relative abundance of beneficial bacteria. MLT may regulate the "arginine-glutathione" pathway, "phenylalanine, tyrosine and tryptophan biosynthesis-tryptophan generation" branch, "tryptophan-kynurenine" metabolism, and "tryptophan-tryptamine-serotonin" pathway through microorganisms.

Effects of defatting and cooking methods on pig large intestines volatile compounds by flavor omics and fatty acids

Pig large intestines (PLIs) are a food with a selective preference globally because of characteristic odors. To investigate the effect of defatting and different cooking methods on the volatile compounds of PLIs, defatted and nondefatted samples were cooked using steaming, water boiling, and frying. A total of 63 volatiles were identified, including 22 compounds detected in all samples. Using odor activity value (OAV) and sensory evaluation, 3-methyl indole and p-cresol, with animal and fecal odors, respectively, were identified as the key off-odors of PLIs. The three cooking methods increased the concentration of aldehydes and endowed samples with fatty and green odors derived from lipid oxidation, especially C18:1n9c and C18:2n6c. Frying significantly increased the content of (E)-2-heptenal and (E,E)-2,4-decadienal (P < 0.05) due to higher contents of C18:2n6c. Compared with steaming and frying, water boiling could significantly reduce the occurrence of off-odors and had the best result combined with defatting. Using orthogonal partial least squares-discriminant analysis (OPLS-DA) and variable importance for the projection (VIP), p-cresol could act as a marker to discriminate samples with different treatments.

Hydrogenation of liquid organic hydrogen carriers: Process scale-up, economic analysis and optimization

Hydrogen has been proposed as energy vector because it can be produced from renewable energy sources and its use produces no carbon dioxide. Moreover, many industrial processes (e.g., steel industry, ammonia, and fertilizer industry, etc.) are also adopting renewable-produced hydrogen as raw material, replacing traditional fossil sources. In this context, the storage and transportation of hydrogen using liquid organic hydrogen carriers (LOHC) is interesting to deal with the discontinuous production of renewable energies.The work addressed the study of the hydrogenation process for three compounds, 3,5-dibenzyl toluene, 2-methyl indole and N-ethylcarbazole, on Ni and Ru-based catalysts. The reactor consisted of a three-phase slurry stirred tank reactor, which has been scale-up together with the rest of the process equipment units using Aspen Hysys simulation software. The hydrogen storage cost has been determined applying an economic evaluation to the overall process. The most important costs of the process are the reactor cost and the cost of raw materials (the liquid organic hydrogen carrier). The main design variables, plant capacity, reactor temperature and pressure, were optimized to reduce the storage cost. The liquid organic hydrogen carrier with the minimum storage cost at the optimum operating conditions is 3,5-dibenzyl toluene with a reactor configuration of two parallel tanks.

Screening of skatole-degrading bacteria and control of human fecal odor by compound bacteria

PurposeThe biodegradation of skatole was used as a starting point in this study, and existing strains of degrading NH3 and H2S in the laboratory were combined to create a composite deodorant. The deodorization effect of the composite deodorant on human feces was investigated in order to provide a foundation for fecal odor gas treatment.MethodsSkatole-degrading bacteria were identified, degradation conditions were optimized, and skatole metabolites were identified using liquid chromatography-mass spectrometry (LC-MS). The skatole-degrading bacteria were combined with the existing strains of degrading NH3 and H2S in the laboratory to make a compound deodorizer, and the deodorizing effect of the compound deodorizer on fresh human feces and old human feces was compared. Liquid chromatography, specific sensors, and gas chromatography were used to determine the contents of skatole, NH3, H2S, and volatile organic compounds, and the microbial diversity was examined.ResultsMicrobial agents H and Y capable of utilizing skatole were screened out under aerobic and facultative anaerobic conditions, respectively. Within 48 h, the degradation rate of skatole by microbial agent Y was 88.52%. Following condition optimization, the optimum temperature for skatole degradation by microbial agent Y was 33 °C, and the optimum pH was 7. The main functional bacteria were Acinetobacter xiamenensis. The metabolites of skatole were determined by liquid chromatography-mass spectrometry (LC–MS), and six possible metabolites were found, including 3-aldehyde indole, 3-carboxyl indole, 1H-indole-2,3-dione, and 3-methyl indole pyruvate. The skatole-degrading bacteria Lactobacillus rhamnosus and Saccharomyces cerevisiae were then combined in proportion to form a composite deodorant. The 5-day degradation rate of skatole in the old manure group was 88.11%, while the 5-day degradation rate in the fresh manure group was 47.56%.ConclusionsThe compound microbial agent developed in this study has a solid deodorizing effect, particularly in the control of the odor of obsolete feces. The use of composite microbial agents can efficiently degrade skatole in human feces, providing a theoretical foundation for the use of microbial remediation in the actual world.Graphical

SYNTHESIS AND ANTICONVULSANT ACTIVITY OF NEWER BENZOTHIAZINYL / BENZOXAZINYL INDOLES

3-Acetyl-2-methyl-indole (1) was synthesized by acetylation of 2-methyl indole with acetyl chloride. Facile condensation of compound (1) with various aromatic aldehydes yielded 1-(2’ -methylindolyl) arylidenyl chalcones (2-7), which on treating with 2-aminothiophenol and 2-aminophenol afforded 2-substitutedphenyl-2,3-dihydro-4-(2’ -methylindolyl)-1,5-benzthiazepines (8-13) and 2-substitutedphenyl-2,3-dihydro-4-(2’ -methylindolyl)-1,5-benzoxazepines (14-19), respectively. The structures of all the compounds were delineated by elemental analysis, IR and proton magnetic resonance. The newly synthesized compounds were evaluated for their anticonvulsant activity and were compared with standard drug phenytoin sodium. These compounds were also tested for acute toxicity. Compound 12 was found to be the most potent compound of the series, exhibiting activity of 90 % more potent than standard drug. Compounds 13 and 18 also showed promising activity of 80 %, equipotent to standard drug.

Thermodynamic Analysis of Chemical Hydrogen Storage: Energetics of Liquid Organic Hydrogen Carrier Systems Based on Methyl-Substituted Indoles.

Liquid organic hydrogen carriers can store hydrogen in a safe and dense form through covalent bonds. Hydrogen uptake and release are realized by catalytic hydrogenation and dehydrogenation, respectively. Indoles have been demonstrated to be interesting candidates for this task. The enthalpy of reaction is a crucial parameter in this regard as it determines not only the heat demand for hydrogen release, but also the reaction equilibrium at given conditions. In this work, a combination of experimental measurements, quantum chemical methods and a group-additivity approach has been applied to obtain a consistent dataset on the enthalpies of formation of different methylated indole derivatives and their hydrogenated counterparts. The results show a namable influence of the number and position of methyl groups on the enthalpy of reaction. The enthalpy of reaction of the overall hydrogenation reaction varies in the range of up to 18.2 kJ·mol-1 (corresponding to 4.6 kJ·mol(H2)-1). The widest range of enthalpy of reaction data for different methyl indoles has been observed for the last step (hydrogenation for the last double bond in the five-membered ring). Here a difference of up to 7.3 kJ·mol(H2)-1 between the highest and the lowest value was found.

Pectin modulates intestinal immunity in a pig model via regulating the gut microbiota-derived tryptophan metabolite-AhR-IL22 pathway

BackgroundPectin is a heteropolysaccharide that acts as an intestinal immunomodulator, promoting intestinal development and regulating intestinal flora in the gut. However, the relevant mechanisms remain obscure. In this study, pigs were fed a corn-soybean meal-based diet supplemented with either 5% microcrystalline cellulose (MCC) or 5% pectin for 3 weeks, to investigate the metabolites and anti-inflammatory properties of the jejunum.ResultThe results showed that dietary pectin supplementation improved intestinal integrity (Claudin-1, Occludin) and inflammatory response [interleukin (IL)-10], and the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) was down-regulated in the jejunum. Moreover, pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets. Pectin specifically increased the abundance of Lactococcus, Enterococcus, and the microbiota-derived metabolites (skatole (ST), 3-indoleacetic acid (IAA), 3-indolepropionic acid (IPA), 5-hydroxyindole-3-acetic acid (HIAA), and tryptamine (Tpm)), which activated the aryl hydrocarbon receptor (AhR) pathway. AhR activation modulates IL-22 and its downstream pathways. Correlation analysis revealed the potential relationship between metabolites and intestinal morphology, intestinal gene expression, and cytokine levels.ConclusionIn conclusion, these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway, which is activated through tryptophan metabolites.

P217 Volatile organic metabolites to predict clinical response to biological therapy in inflammatory bowel disease

Abstract Background Volatiles organic metabolites (VOMs) are a large group of carbon-bound chemicals elements, gaseous at room temperature that are the products of metabolism. There is increasing evidence that variations in faecal VOMs indicate gastroenterological diseases. No study assessed VOMs in the setting of predicting therapeutic response in inflammatory bowel disease (IBD). Methods We conducted a prospective study in which we consecutively recruited IBD patients with indications for treatment with biologics. The primary outcome of our study was the evaluation of prediction ability of VOMs of clinical response at 12 months of adalimumab or vedolizumab therapy. Secondary outcomes included correlations of VOM with clinical features of IBD. Results We recruited 50 patients with IBD whose stools were analysed with gold standard technique mass spectrometer (MS) / gas chromatography (GC). Thirty-one patients were treated with adalimumab (of which 30 Crohn’s disease, and 1 ulcerative colitis, UC), 19 patients with vedolizumab (of which 12 CD and 7 UC). VOMs were not influenced by age, disease duration, sex, smoking habit. Two VOMs, octenol and, in particular, methyl indole were able to distinguish ulcerative colitis (UC) from Crohn’s disease (CD) (AUC = 0.72 and 0.85, respectively) and correlate with higher inflammation markers (C-reactive protein, CRP and calprotectin, respectively). Methylbutanal, instead, was a marker of CD and, in particular, of ileal location (p = 0.01). These results were confirmed at principal component analysis (PCA). Lower levels of ethanol and methyl butanoate correlated with disease remission. Methyl butanoate was able to distinguish remission from active clinical disease, with an accuracy at least equal to that of calprotectin (AUC = 0.69 and AUC = 0.62, respectively). We furthermore demonstrated pre-biologics methyl butyrate prediction ability of clinical response after 12 months of therapy (AUC = 0.68, 95%CI = 0.53-0.81, p = 0.02). Lower levels of methyl indole or of octenol or higher levels of indole were able to predict calprotectin &amp;lt;250 mg/kg without steroid at month 12; undetectable levels of basal ethyl butanoate correlated with calprotectin &amp;lt;250 mg/kg without steroid at month 12 (p = 0.04) in the subgroup of patients treated with vedolizumab, while higher levels of ethyl butanoate correlate with higher CRP levels. Our finding of a lower piperidone level in patients undergoing previous bowel resection is consistent with literature data that found an association between active CD and higher piperidone levels. Conclusion The characterization of the intestinal metabolome, using VOMs technology, seems to be a promising method for better characterizing IBD and better speculating on their etiopathogenesis.

Arbuscular mycorrhizal colonization leads to a change of hormone profile in micropropagated plantlet Satureja khuzistanica Jam

Phytohormones are supposed to contribute to the establishment of mutualistic Arbuscular mycorrhiza (AM) symbioses. However, their role in the acclimation of micropropagated plantlet inoculated with AM is still unknown. To address this question, we performed a hormone profiling during the acclimation of Satureja khuzistanica plantlets inoculated with Rhizoglomus fasciculatum. The levels of indoleacetic acid (IAA), methyl indole acetic acid, cis-zeatin, cis zeatin ribose, jasmonate, jasmonoyl isoleucine, salicylic acid, abscisic acid (ABA) were analyzed. Further, the relative gene expression of AOS (Allene oxide synthase) as a key enzyme of jasmonate biosynthesis, in either inoculated or non-inoculated micropropagated plantlets was evaluated during acclimation period. The concentrations of IAA and cis-zeatin increased in the plantlets inoculated by AM whereas the concentration of ABA decreased upon 60 days acclimation in the whole shoot of plantlets of S. khuzistanica. The relative expression of AOS gene resulted in an increase of isoleucine jasmonate, the bioactive form of jasmonate. Based on our results, IAA and cis-zeatin probably contribute to maintaining growth, and AM reduces transition stress by modifying ABA and jasmonate concentrations.

Phytochemical profiling of antimicrobial and potential antioxidant plant: Nepeta cataria.

Traditional and phytochemical studies have confirmed the richness and diversity of medicinal plants such as Nepeta cataria (N. cataria), but more studies are needed to complete its metabolite profiling. The objective of this research was to enhance the metabolomic picture and bioactivity of N. cataria for better evaluation. Phytochemical analysis was performed by bio-guided protocols and gas chromatography-mass spectrometry (GC/MS). For this, solvents such as methanol, ethanol, water, acetone, and hexane were used to extract a wide number of chemicals. Antibacterial analysis was performed using the 96-well plate test, Kirby Bauer's disk diffusion method, and the resazurin microdilution test. Antioxidant activity was determined by the DPPH assay and radical scavenging capacity was evaluated by the oxygen radical absorbance capacity (ORAC) assay. GC/MS analysis revealed a total of 247 identified and 127 novel metabolites from all extracts of N. cataria. Water and acetone extracts had the highest identified metabolites (n = 79), whereas methanol extract was the highest in unidentified metabolites (n = 48). The most abundant phytochemicals in methanol extract were 1-isopropylcyclohex-1-ene (concentration = 27.376) and bicyclo [2.2.1] heptan-2-one (concentration = 20.437), whereas in ethanol extract, it was 9,12,15-octadecatrienoic acid (concentration = 27.308) and 1-isopropylcyclohex-1-ene (concentration = 25.854). An abundance of 2 methyl indoles, conhydrin, and coumarin was found in water extracts; a good concentration of eucalyptol was found in acetone extract; and 7,9-di-tert-butyl-1-oxaspiro is the most abundant phytochemicals in hexane extracts. The highest concentration of flavonoids and phenols were identified in hexane and methanol extracts, respectively. The highest antioxidant potential (DPPH assay) was observed in acetone extract. The ethanolic extract exhibited a two-fold higher ORAC than the methanol extract. This examination demonstrated the inhibitory effect against a set of microbes and the presence of polar and non-polar constituents of N. cataria. The results of this study provide a safe resource for the development of food, agriculture, pharmaceutical, and other industrial products upon further research validation.

Tin (IV) chloride catalysed synthesis of di(indolyl)methanes during electrophilic substitution of indoles and 2-methyl indoles

An efficient methodology has been developed for the synthesis of di(indolyl)methanes in moderate to good yields during the study of the reactions of indole and 2-methyl indole using a series of aliphatic ketones in the presence of stannic chloride. It appears worth mentioning that with 2-methyl indole and acetone and ethyl methyl ketone the highly “elusive” indolylcarbinols, the postulated intermediates in the synthesis of di(indolyl)methanes, have been isolated.

Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is a nosocomial pathogen associated with urinary tract infections and expresses several virulence factors that cause recurring infections and cystitis of the bladder, which can lead to pyelonephritis. UPEC uses different types of extracellular appendages like fimbriae and pili that aid colonization and adherence to bladder epithelium and can form persistent biofilm-like bacterial communities that aid its survival after the deployment of host immune responses. We investigated the antibiofilm, antimicrobial, and antivirulence properties of three indole derivatives namely, 4-chloroindole, 5-chloroindole, and 5-chloro 2-methyl indole. All the three chloroindoles had MICs of 75 μg/ml and inhibited biofilm formation by an average of 67% at 20 μg/ml. In addition, they inhibited swarming and swimming motilities, which are essential for dissemination from bacterial communities and colonization, reduced cell surface hydrophobicity, and inhibited indole production and curli formation. Gene expression analysis showed all three chloroindoles significantly downregulated the expressions of virulence genes associated with adhesion, stress regulation, and toxin production. A 3D-QSAR analysis revealed substitutions at the fourth and fifth positions of the indole moiety favored antimicrobial activity. Furthermore, these chloroindoles potently inhibited biofilm formation in other nosocomial pathogens and polymicrobial consortia.

Indazole MRL-871 interacts with PPARγ via a binding mode that induces partial agonism

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays a central role in metabolic processes. PPARγ full agonists have side effects, arguing for the discovery of PPARγ partial agonists with novel chemotypes. We report the unique binding mode of the known allosteric retinoic acid receptor-related orphan receptor gamma t (RORγt) ligand MRL-871 to PPARγ. MRL-871 binds between PPARγ helices 3, 5, 7 and 11, where it stabilizes the beta-sheet region with a hydrogen bond between its carboxylic acid moiety and PPARγ Ser370. Its unique binding mode differs from that of the benzoyl 2-methyl indoles which are well-studied, structurally similar, PPARγ ligands. MRL-871′s high affinity for PPARγ induces only limited coactivator stabilization, highlighting its attractive partial agonistic characteristics. Affinity comparison of MRL-871 and related compounds towards both RORγt and PPARγ indicates the possibility for tuning of selectivity, bringing MRL-871 forward as an interesting starting point for novel PPARγ ligands.

Synthesis and anticancer screening of some novel Pd-catalysed 3-methyl indole based analogues on Mia PaCa-2 cell line

Indole is a most prerogative moiety in the evaluation of anticancer agents for its versatility and bio-diversity. The indole based compounds have been reported by the researchers in the last decade with potent anticancer activities. The coupled indole ring system with other biodynamic moieties is known to increase the bio-efficiency. Hence, a series of 3-methyl-indole-2-pyrindine coupled secondary amines have been synthesized via Suzuki-Miyaura and Buchwald Hartwig coupling. The compounds 9a-e have been docked against Hypoxia-inducible factor 1α (HIF-1α) enzyme to demonstrate the binding interactions with the active site, shown the binding affinity from -7.5 to -8.1 Kcal/mol and disclosed the potentiality of synthesized compounds to bind and inhibits the HIF-1α (Pdb Id: 3KCX) pathway and predicted several in silico ADMET descriptors for the 3-methyl Indole analogues. The molecules were screened for their anti-pancreatic cancer activity and tested against Mia PaCa-2 cell line by MTT assay, revealed that; compound 9d exhibited a greater antiproliferation activity in the series, with IC50 of 73.63±2.05 µM. Our present findings revealed that 9d might be a pursuable lead for further anti-pancreatic cancer studies.

Consumer evaluation of meat quality from barrows, immunocastrates and boars in six countries

The practice of surgical castration of piglets and its alternatives is still under debate. Production of boars may impair meat quality due to boar taint and reduced tenderness compared to meat from surgically castrated male pigs, while immunocastration reduces boar taint and may improve meat quality but seems to be less accepted by the pig chain. In this study, we aimed to evaluate the consumer’s sensory appreciation of meat from barrows (BAs), immunocastrates (ICs) and boars (BOs) in six European countries, taking into account the selection of tainted carcass and consumers’ appreciation of boar taint. Loin chops of 30 BAs, 30 ICs and 30 BOs were evaluated by 752 consumers in six countries: Belgium, Czech Republic, Poland, Portugal, Romania and Spain. Consumers rated odour, flavour, tenderness, juiciness, overall liking and willingness to buy and sensitivity to and liking of androstenone (AND) and liking of skatole (SKA) was also tested. In each of the six countries, consumers liked the odour of the BO samples less than that of BA, and IC intermediate. For flavour, tenderness, juiciness, overall liking and willingness to buy, liking scores given by the Czech, Polish and Portuguese consumers significantly differed between the BA, BO and IC. Willingness to buy was highest for BA by Czech and Polish consumers and for BA and IC by Portuguese consumers. The frequency of the negative check all terms that apply terms also differed, with a higher frequency of disgusting for BO compared to BA and IC and of off-flavour, irritating, manure, sweat, disappointing compared to BA, and intermediate for IC. 31% of the consumers disliked the odour of AND (NEGAND), and 36% of them were not sensitive; in contrast, 77% of the consumers disliked SKA (NEGSKA). The decrease in flavour liking score for BO compared to BA and IC was more outspoken by the NEGAND consumer, while NEGSKA consumers gave an overall lower liking score independent of the type of male pig. The results of this study indicate that IC can be a valid alternative for surgical castration.