Search

2-Thiazolines are important building blocks in organic synthesis and are of great importance in many areas of chemistry. At the end of the last century, the use of 2-thiazolines increased in a significant way, especially in synthesis and catalysis. This review highlights the synthetic and catalytic value of 2-thiazolines in the last two decades. We will discuss the new synthetic methodologies for obtaining these heterocycles including new schemes for accessing their asymmetric versions. Most of the new catalytic applications include a variety of 2-thiazoline ligands containing diverse donor atoms, which in combination with metals like Pd, Ir, and Cu, among others, exhibit remarkable catalytic performances.

All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1,2,3,4, a phenomenon that occurs in hypoxia4,5,6,7,8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism., This research has been financed by Spanish Government grants (ISCIII and AEI agencies, partially funded by the European Union FEDER/ERDF) CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme to A.M.-R. and J.A.E.); CP07/00143, PS09/00101, PI12/00875, PI15/00107 and RTI2018-094203-B-I00 (to A.M.-R.); CP12/03304 and PI15/01100 (to L.M.); CP14/00008, CPII19/00005 and PI16/00735 (to J.E.); SAF2016-77222-R (to A. Cogolludo); PI17/01286 (to P.N.); SAF2015-65633-R, RTI2018-099357-B-I00 and CB16/10/00282 (to J.A.E.); RTI2018-095793-B-I00 (to M.G.L.); and SAF2017-84494-2-R (to J.R.-C.), by the European Union (ITN GA317433 to J.A.E. and MC-CIG GA304217 to R.A.-P.), by grants from the Comunidad de Madrid B2017/BMD-3727 (to A. Cogolludo) and B2017/BMD-3827 (to M.G.L.), by a grant from the Fundación Domingo Martínez (to M.G.L. and A.M.-R.), by the Human Frontier Science Program grant HFSP-RGP0016/2018 (to J.A.E.), by grants from the Fundación BBVA (to R.A.-P. and J.R.-C.), by the UCM-Banco Santander grant PR75/18-21561 (to A.M.-d.-P.), by the Programa Red Guipuzcoana de Ciencia, Tecnología e Información 2018-CIEN-000058-01 (to J.R.-C.) and from the Basque Government under the ELKARTEK Program (grant no. KK-2019/bmG19 to J.R.-C.), by the Swiss National Science Foundation (SNF) grant 310030_124970/1 (to A.B.), by a travel grant from the IIS-IP (to P.H.-A.) and by the COST actions TD0901 (HypoxiaNet) and BM1203 (EU-ROS). The CNIC is supported by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (Spanish Government award SEV-2015-0505). CIC biomaGUNE is supported by the María de Maeztu Units of Excellence Program from the Spanish Government (MDM-2017-0720). P.H.-A. was a recipient of a predoctoral FPU fellowship from the Spanish Government. E.N. is a recipient of a predoctoral FPI fellowship from the Universidad Autónoma de Madrid (UAM). A.M.-R., L.M. and J.E. are supported by the I3SNS or ‘Miguel Servet’ programmes (ISCIII, Spanish Government; partially funded by the FEDER/ERDF).

Mexico has an enormous diversity of Agave species. The agave sap (called aguamiel) is concentrated to obtain a syrup. In this study, the aguamiel was obtained from two different Agave species: A. salmiana and A. atrovirens, then it was concentrated using four different temperature treatments (70 °C, 80 °C, 90 °C, and 95 °C). During thermal processing, the chemical, proximal, and sweetness analyses were determined. The temperature affected the color, samples treated at 70 °C and 80 °C were the darkest. The pH of the syrups was acidic (4.15 to 5.47). The moisture of the samples remains constant (ca. 40%). The fat value in the samples was under 1.3%, and the fiber was not detected in any of the samples. The A. salmiana syrup had the highest ash content (8%), A. atrovirens contain 50% less. In protein content, A. atrovirens syrups presented 8.5% and A. salmiana nearly 3%. The 5-hydroxymethyl-furfural was not affected by any of the used temperatures. A. atrovirens syrups contained more glucose (ca. 23%). The temperature affected the sucrose content; it was higher at 70 °C. The samples revealed the content of fructooligosaccharides, such as 1-kestose, 1-nystose, and 1-fructofuranosyl nystose. 1-nystose was detected only in A. salmiana syrups. The food analysis of these syrups was essential to understand the effect of the Agave species and temperature treatments used during the production of agave syrup.

A new family of push-pull biphenyl-azopyrrole compounds 3b-g and 4b-d was efficiently obtained via a Suzuki cross-coupling reaction between 2-(4'-iodophenyl-azo)-N-methyl pyrrole (1a) or 3-(4'-iodophenyl-azo)-1,2,5-trimethyl pyrrole (2a) and 4'-substituted phenyl boronic acids in excellent yields. The influence of the π-biphenyl backbone and pyrrole pattern substitution was correlated with their optical properties. Solvatochromic studies via UV-visible spectrophotometry revealed that the inclusion of a 4'-nitro-biphenyl fragment favors a red-shift of the main absorption band in these azo compounds compared with their non-substituted analogues. Likewise, optical band-gaps were estimated by means of electronic absorption spectra and correlated with TD-DFT studies. The pyrrole pattern substitution and the π-conjugated backbone exhibit a clear influence on their thermal isomerization kinetics at room temperature. In all cases, biphenylazo-pyrrole compounds lead to the formation of J-type aggregates in binary MeOH : H2O solvents. Under these conditions, compounds 3b-c undergo a water-assisted cis-to-trans isomerization at room temperature.

A set of alkyl aluminum complexes supported by non-symmetric ferrocenyl amidine ligands were used as catalysts for the preparation of cyclic carbonates from epoxides and carbon dioxide using Bu4NI as a co-catalyst. A modified method for the synthesis of aminoferrocene allowed us to obtain this precursor in quantitative yield. Treatment of aminoferrocene with the corresponding acetimidoyl chloride afforded the desired ferrocenyl amidine ligands L1H, (E)-N-(2,6-diisopropylphenyl)-N’-(ferrocenyl)acetimidamide, and L2H, (E)-N-(2,6-dimethylphenyl)-N’-(ferrocenyl)acetimidamide. The reaction of these ligands with 1.0 or 0.5 equiv. of AlMe3 led to the synthesis of aminoferrocene based aluminum complexes ((L1)AlMe2 (1), (L2)AlMe2 (2), (L1)2AlMe (3), and (L2)2AlMe (4)) in excellent yields, which were characterized by spectroscopic and X-ray diffraction methods. In addition, we have studied their electrochemical properties and complex 1 was found to be the most active catalyst for the formation of cyclic carbonates 6a–j from their corresponding epoxides 5a–j and CO2.

Aims Profiling of lipoproteins can predict risk of cardiovascular disease; gel permeation high-performance liquid chromatography (HPLC) improves prediction accuracy by providing detailed data for specific lipoprotein subclasses. This study applied HPLC to examine the effects of evolocumab, which effectively treats hyperlipidemia and mixed dyslipidemia, on lipoprotein subclasses, specifically the number and size of lipoprotein particles. Methods This post-hoc analysis used patient blood samples from YUKAWA-2, a phase 3 trial evaluating the efficacy of evolocumab in Japanese adult patients with hyperlipidemia or mixed dyslipidemia and at high risk for cardiovascular disease. We used HPLC to assess observed values and percent change from baseline in cholesterol and triglyceride (TG) concentrations, number of particles in lipoprotein subclasses to week 12, and mean observed values and mean percent change from baseline in variables to weeks 10 and 12. HPLC was also compared with conventional methods in assessing low-density lipoprotein (LDL) cholesterol (LDL-C) values. Results Data for all 404 patients were analyzed. Evolocumab significantly decreased cholesterol and TG concentrations, and total particle count, in very low-density lipoprotein (VLDL) and LDL subclasses. Particle size increased slightly in LDL, high-density lipoprotein (HDL), and VLDL, but data varied widely. At very low LDL-C, HPLC measurements were higher than those from conventional methods. Conclusion This research used HPLC to assess the effects of evolocumab in 20 lipid subclasses. By lowering lipid content and improving the lipid profile, evolocumab may reduce atherogenicity. This reduction is better quantified by HPLC than by conventional methods in the very low LDL-C range.

Introduction/Background* The goal of this study is to review the sentinel lymph node (SLN) in endometrial cancer in the University Hospital 12 de Octubre in Madrid from June 2016 to October 2020. The aim is to know the demographic and clinical features of the patients and to assess the outcomes of SLN in our population with technetium99 (Tc99), indocyanine green (ICG) or blue dye. Methodology Result(s)* From June 2016 to October 2020, 166 patients diagnosed with endometrial cancer underwent surgery in our hospital. In 34.4% (n= 57) of them SLN was performed and included in this review. Demographic and clinical features are shown in table 1. 80.7% (n=46) were classified as low risk endometrial cancer and 19,3% (n=11) as intermediate risk. Laparoscopy was the most frequent approach (96.4%). Median operative time was 203 minutes (IQR, 173 to 249). A combined tracer technique was used in 75.4% cases. Most of them combining Tc99 and ICG (64.9%). Tc99 and blue dye were used in 10.5%. Only one tracer was used in 24.6% (Tc99 5.3%; ICG 17.5%; blue dye 1.8%). Cervix was the only injection site into submucosa and stroma. In 89.5% of the patients, tracer migration was observed. Only 6 patients (10.5%) had no migration. In table 2, detection and migration data of the tracers are shown. One hundred forty-four SLNs were detected. Right side (52.8%) was slightly more frequent than left side (47.2%). Most SLNs were located in external iliac area (40.5%), followed by iliac bifurcation (25.3%), obturator fossa (17.7%) and common iliac (13.9%). In three patients isolated tumor cells were detected (5.2%) and one patient had macrometastases (1.8%). 93% of the patients had no pathological findings in SLNs. Age was significantly higher in the no migration/no detection group in both Tc99 (70 vs 58.5 years; p= 0.01) and ICG/blue dye (72.5 vs 59.4 years; p=0.034). No migration/detection differences were detected for other patient´s features. Conclusion* A combined tracer technique is an effective method to detect SLNs in low-risk endometrial cancer to check lymphatic spread. Older women in our series have lower tracer migration/detection.

The participation of non-Saccharomyces yeasts in fermentation processes is of great importance due to their participation in the formation of esters and superior alcohols, which confer characteristic aromas to beverages such as wine and mescal. The aim of this study was identify and evaluate the potential aroma production of yeast native of Agave fermentation by the mescal production in Durango, Mexico. Isolated yeasts were molecularly identified by 5.8s ribosomal gene; the potential production of aromas was carried out in fermentations with the addition of l-phenylalanine and evaluated after 24 h of fermentation. Extraction and quantification of aromatic compounds by headspace solid-phase micro-extraction (HS-SPME) and gas chromatograph mass spectrometry (GC-MS). The isolated non-Saccharomyces yeasts could be classified into six different genera Saccharomyces cerevisiae, Clavispora lusitaniae, Torulaspora delbrueckii, Kluyveromyces dobzhanskii, Kluyveromyces marxianus, and Kluyveromyces sp. All probed strains presented a potential aroma production (ethyl acetate, isoamyl acetate, isoamyl alcohol, benzaldehyde, 2-phenylethyl butyrate, and phenylethyl propionate), particularly 2-phenylethanol and 2-phenylethylacetate; the levels found in the Kluyveromyces marxianus ITD0211 yeast have the highest 2-phenylethylacetate production at 203 mg/L and Kluyveromyces marxianus ITD0090 with a production of 2-phenylethanol at 1024 mg/L. Non-Saccharomyces yeasts were isolated from the mescal fermentation in Durango; the Kluyveromyces genus is the most predominant. For the production of aromas, highlighting two strains of Kluyveromyces marxianus produces competitive quantities of compounds of great biotechnological interest such as 2-phenylethanol and 2-phenylethylacetate, without resorting to the genetic modification of yeasts or the optimization of the culture medium.

Protein aggregation has been observed inside cells and holds true for membraneless organelles. The precise understanding of protein dimerization is a prerequisite for manipulating protein aggregation, which is promising for elevating enzyme concentration to enhance their catalytic performance. Here, the dimerization of two industrially important enzymes of cytochrome P450 (P450) and organophosphorus hydrolase (OPH) is investigated using all-atom explicit solvent molecular dynamics simulations, umbrella sampling, and protein-protein docking calculations. The calculated potentials of mean force of dimer-monomer dissociation demonstrate that the dimeric forms are more stable with the free energy barrier of around 60 kJ/mol for P450 and 101 kJ/mol for OPH. The docking calculations on the OPH dimer evidence the uniqueness of the native orientation. The protein dimers form "mirror"-like orientations with some degree of rotation. Such signature orientations are interpreted based on the predominant polar amino acids in the contact regime. In the dimer conformations, the active sites are exposed. This work highlights the crucial roles of the polar and nonpolar protein surface domains to form enzymatically active protein dimer aggregates. Our work will potentially aid the design of molecules that can deliver and protect native protein function in various environments.

We report an efficient synthesis of new non-symmetric pincer palladacycles 2a–i, containing a [NNC]-tridentate ligand formed by a hydrazone and a thiazolyl moiety as sources of N-donor atoms. These catalytic precursors were tested in the Suzuki–Miyaura cross coupling reaction using a variety of aryl boronic acids with aryl bromides or chlorides using water as solvent. Complex 2a displays the best catalytic performance under aerobic conditions, affording the coupling products in good to high yields. In all cases, the cross-coupling reaction was conducted under IR irradiation, allowing a decrease in the reaction time.

Background Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM. Methods This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD. Results In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C 75% achieved non-HDL-C 67% achieved ApoB Conclusions Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.

In the pharmaceutical industry nano-hydrocolloid systems frequently coalesce or present nanoparticle aggregation after a long storage periods. Besides, the lyophilization process used to dry nanoparticles (NPs) produces loss of their original properties after dispersion. In this work we evaluated the effect on morphology and physicochemical properties of different protective excipients during drying of bovine serum albumin (BSA) NPs loaded with different concentrations of capsaicin. Capsaicin concentrations of 0, 812, 1625, 2437, and 3250 µg mL−1 were used; subsequently, NPs were dried with deionized water (DW), NaCl (DN), sucrose (DS), and not dried (ND). We found that ND, DW, and DN treatments showed a negative effect on the NPs properties; while, DS reduced the aggregation and produced the formation of isolated nanoparticles at higher concentrations of capsaicin (3250 µg mL−1), improving their circular shape, morphometrical parameters, and ζ-potential. The stability of the BSA-capsaicin NPs was associated to complex capsaicin/amino acid/water, in which GLY/GLN, ALA/HIS, ARG, THR, TYR, and Iso/CYS amino acids are involved in the restructuration of capsaicin molecules into the surface of nanoparticles during the drying process. The secondary nanostructuration in the post-synthesis stage can improve the molecular stability of the particles and the capacity of entrapping hydrophobic drugs, like capsaicin.

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are im-plicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroven-tricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice., This work was supported by the Spanish Ministry of Science, innovation and Universities Ref. SAF2015-63935-R and Ref. RTI2018-095793-B-I00 and General Council for Research and Innovation of the Community of Madrid and European Structural Funds Ref. B2017/BMD–3827–NRF24ADCM to M.G.L. Aging studies were supported by an NIA grant (R01-AG-033028) to J.P.G .

Nanoparticles (NP) of 12.7 nm in diameter of the poly(methyl methacrylate (MMA)-co-methacrylic acid (MAA)) copolymer were prepared. 13C-NMR results showed a MMA:MAA molar ratio of 0.64:0.36 in the ...

This study investigated Lippia palmeri Watt (oregano) phytochemical compounds, their antioxidant capacity, and immunological effects on goat peripheral blood leukocytes (PBL), and on the presence of intermediate polar compounds in goat feces fed dietary oregano. The polar and nonpolar fractions of L. palmeri W. were characterized and phytochemical contents and antioxidant capacity were determined. Twelve healthy Anglo-Nubian goats were used for the in vivo trials, which were randomly assigned to control fed with basal diet, or oregano group fed with basal diet + 2.6% (DM basis) dried oregano leaves. Goat peripheral blood leukocytes (PBL) were isolated for the in vitro study, and PBL were stimulated with oregano extracts at 100 and 150 μg/mL after 24 h. For the in vivo trial, dietary oregano (2.6% on DM basis) was evaluated in the goats for 90 days. Relatively high abundance of carvacrol and thymol phytochemical compounds was found in oregano. The highest antioxidant capacity of oregano extracts was detected at 100 and 150 μg/mL. Nitric oxide production, phagocytosis, and superoxide dismutase activities increased (p

International audience; A method for the synthesis of a new phosphine-free [N,N,O]-tridentate Schiff base ligand L1 using the 2-Ferrocenyl-2-thiazoline as scaffold was developed. The 1,2-disubstituted ferrocene-based ligand was assembled using as key strategy the directed ortho-metalation (DoM) in 2-ferrocenyl-2-thiazoline. L1 was successfully obtained in 83% of overall yield after two-step synthesis. The coordination ability of L1 towards Ru(II) was evidenced and the resulting complex was characterized by IR, UV-vis and EPR. Its catalytic performance was tested in transfer hydrogenation of a variety of substrates giving moderate to excellent conversions.

Lavender oil- (LO-) loaded ultrafine nanoparticles (NP) ( diameter < 50 nm ) of a copolymer were used for impregnating fabrics of cotton, cotton polyester, and polyester-elastane. The copolymer was composed mainly of methyl methacrylate (MMA) units with a low proportion of methacrylic acid (MAA). Moreover, two kinds of NP were used: one containing uncrosslinked copolymer and another one composed of crosslinked material. All the fabrics impregnated with NP of uncrosslinked copolymer keep the aroma up to 25 washes. Under storage at ambient conditions, the fabrics impregnated with NP of either uncrosslinked or crosslinked copolymer emitted aroma for up to almost 60 days. The long duration of aroma emission from fabrics is attributed to ease of the small nanoparticles used in this study of penetrating and staying inside the pores of the fabric fibers.

Highly branched neo-fructans (agavins) are natural prebiotics found in Agave plants, with a large capacity to mitigate the development of obesity and metabolic syndrome. Here, we investigated the impact of agavins intake on gut microbiota modulation and their metabolites as well as their effect on metabolic endotoxemia and low-grade inflammation in mice fed high-fat diet. Mice were fed with a standard diet (ST) and high-fat diet (HF) alone or plus an agavins supplement (HF+A) for ten weeks. Gut microbiota composition, fecal metabolite profiles, lipopolysaccharides (LPS), pro-inflammatory cytokines, and systemic effects were analyzed. Agavins intake induced substantial changes in gut microbiota composition, enriching Bacteroides, Parabacteroides, Prevotella, Allobaculum, and Akkermansia genus (LDA > 3.0). l-leucine, l-valine, uracil, thymine, and some fatty acids were identified as possible biomarkers for this prebiotic supplement. As novel findings, agavins supplementation significantly decreased LPS and pro-inflammatory (IL-1α, IL-1β, and TNF-α; p < 0.05) cytokines levels in portal vein. In addition, lipid droplets content in the liver and adipocytes size also decreased with agavins consumption. In conclusion, agavins supplementation mitigate metabolic endotoxemia and low-grade inflammation in association with gut microbiota regulation and their metabolic products, thus inducing beneficial responses on metabolic disorders in high-fat diet-fed mice.

Objective: Several studies have linked metabolic syndrome to the development of osteoarthritis (OA) through hypercholesterolemia, one of its components. However, epidemiological studies showed contradictory results, and it is not clear how hypercholesterolemia itself, or oxidized LDL (oxLDL)-a pathological molecule potentially involved in this relationship-could be affecting OA. The objectives of this study were to investigate the effect of hypercholesterolemia induced by high-fat diet (HFD) in cartilage from OA rabbits, and how oxLDL affect human chondrocyte inflammatory and catabolic responses. Design: New Zealand rabbits were fed with HFD for 18 weeks. On week 6, OA was surgically induced. At the end of the study, cartilage damage and IL-1β, IL-6, MCP-1, MMP-13, and COX-2 expression in articular cartilage were evaluated. In addition, cultured human OA articular chondrocytes were treated with oxLDL at concentrations equivalent to those expected in synovial fluid from HFD rabbits, in the presence of IL-1β and TNFα. The effect of oxLDL on cell viability, nitric oxide production and catabolic and pro-inflammatory gene expression was evaluated. Results: HFD intake did not modify cartilage structure or pro-inflammatory and catabolic gene expression and protein presence, both in healthy and OA animals. OxLDL did not affect human chondrocyte viability, ADAMTS5 and liver X receptor (LXR) α gene expression, but decreased the induction of IL-1β, IL-6, MCP-1, MMP-13, iNOS, and COX-2 gene expression and MMP-13 and COX-2 protein presence, evoked by cytokines. Conclusions: Our data suggest that cholesterol intake per se may not be deleterious for articular cartilage. Instead, cholesterol de novo synthesis and altered cholesterol metabolism could be involved in the associations observed in human disease.

The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly spread globally, infecting millions and killing hundreds of thousands of people. Herein, to identify potential antiviral agents, 97 natural amide-like compounds known as alkamides and piperamides were tested against SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), and the human angiotensin-converting enzyme 2 (ACE2) using molecular docking and molecular dynamics simulations. The docking results showed that alkamides and dimeric piperamides from Piper species have a high binding affinity and potential antiviral activity against SARS-CoV-2. The absorption, distribution, metabolism, and excretion (ADME) profile and Lipinski’s rule of five showed that dimeric piperamides have druglikeness potential. The molecular dynamics results showed that pipercyclobutanamide B forms a complex with Mpro at a similar level of stability than N3-I. Our overall results indicate that alkamides and piperamides, and specifically pipercyclobutanamide B, should be further studied as compounds with SARS-CoV-2 antiviral properties.

International audience; P-pyrrole phosphines (R2Ppyr), in which a pyrrole group is directly bonded to the phosphorus atom, act as monodentate k-P ligands towards gold(I) center to afford either neutral or cationic mononuclear complexes as well as neutral dinuclear complexes. All of these new gold(I) complexes have been structurally characterized and their first uses in catalysis have demonstrated their effectiveness as precatalysts for the enyne cycloisomerization reactions.

[EN] Truxene-based porous polymers synthesized through the simple “solvent knitting” strategy from hexamethyl or tribenzyl truxene-based monomers (TxPP1 and TxPP2), and their corresponding TxPP@TiO2 hybrids are used as photocatalysts for H2 production from water using methanol as sacrificial agent, under UV-Vis light. These polymers present higher hydrogen evolution rate (HER) than TiO2, and remarkable thermo- and photo-stabilities. Hybrids TxPP-TiO2 exhibited intensely enhanced photocatalytic activity compared to TiO2 or TxPPs alone. In the presence of platinum (1%) as cocatalyst, HER from TxPP1@T-10 significantly boosted reaching values above 21000 μmol.g-1.h-1 which to the best of our knowledge, represents the highest HER reported for hybrids based on TiO2 and conjugated porous polymers. Interestingly, small structural differences of the corresponding truxene monomers result in different photocatalytic behavior. We focused here on gaining insight on the charge transfer mechanism and rationalizing the different photocatalytic performances in order to establish clear structure-activity relationships. In fact, photoluminescence and transient absorption spectroscopy demonstrated that the remarkably enhanced photocatalytic activity of the most active hybrids (TxPP1@TiO2) can be attributed to the efficiently photogenerated electron-hole separation by a direct Z-scheme mechanism, while lower performance of TxPP2@TiO2, is probably due to a less efficient heterojunction type II charge transfer mechanism., Authors acknowledge to MINECO/AEI/FEDER, UE of Spain (Projects MAT2017-82288-C2-2-P, CTQ2016-78557-R and ENE2016-79608-C2-1-R) and regional government of “Comunidad de Madrid” and European Structural Funds for their financial support to FotoArt-CM project (S2018/NMT-4367). AVG thanks Ministerio de Educación y Formación Profesional for FPU17/03463, M. L and M. B thank to MINECO and European Social Fund for a Ramón y Cajal grant (RyC-2015-18677) and Juan de la Cierva Formación grant (FJCI-2016-30567) respectively.

New multi-target indole and naphthalene derivatives containing the oxadiazolone scaffold as a bioisostere of the melatonin acetamido group have been developed. The novel compounds were characterized at melatonin receptors MT1R and MT2R, quinone reductase 2 (QR2), lipoxygenase-5 (LOX-5), and monoamine oxidases (MAO-A and MAO-B), and also as radical scavengers. We found that selectivity within the oxadiazolone series can be modulated by modifying the side chain functionality and coplanarity with the indole or naphthalene ring. In phenotypic assays, several oxadiazolone-based derivatives induced signalling mediated by the transcription factor NRF2 and promoted the maturation of neural stem-cells into a neuronal phenotype. Activation of NRF2 could be due to the binding of indole derivatives to KEAP1, as deduced from surface plasmon resonance (SPR) experiments. Molecular modelling studies using the crystal structures of QR2 and the KEAP1 Kelch-domain, as well as the recently described X-ray free-electron laser (XFEL) structures of chimeric MT1R and MT2R, provided a rationale for the experimental data and afforded valuable insights for future drug design endeavours, The authors gratefully acknowledge the following financial supports: Spanish Ministry of Science, Innovation and Universities; Spanish Research Agency; and European Regional Development Funds (grants RTI2018-093955-B-C21 and SAF2015-64948-C2-1-R to M.I.R.-F.; RTI2018-095793-B-I00 to M.G.L., SAF2015-64629-C2- 2-R to F.G.), General Council for Research and Innovation of the Community of Madrid and European Structural Funds (grant B2017/BMD-3827 e NRF24ADCM), Health Institute Carlos III (Miguel Servet II ProgramCP16/00014 and grant PI17/01700 to R.L.). CH-A and P.M. thank their PhD fellowships from Spanish Ministry of Education (MEC, PhD grant FPU16/01704 and mobility grant FPUEST17/00233 to CH-A and FPU13/03737 to P.M.).

Activation of aryl(Ar)-halides for C C coupling catalytic reactions using visible light has become one of the most challenging tasks in organic synthesis since it offers effective and safer alternatives to traditional dehalogenation protocols. The insufficient energy provided by visible light to cleave such strong C H alogen bonds certainly makes necessary the development of new protocols to overcome this limitation. We report here the application of photon upconversion (UC) technology based on triplet-triplet annihilation (TTA) to a C C coupling catalytic reaction, a possibility that has not been investigated to date. This synchronized biphotonic process (TTA-UC) activates successfully Ar-halides with visible light. Based on product analysis and spectroscopic experiments, a cascade process combining photophysical and photochemical steps is proposed for the mechanism rationalization. Visible light, ambient temperature and pressure, low-loading metal-free photocatalysts and no additives make this protocol very attractive for applications to the synthesis of fine chemical building blocks, pharmaceuticals, agrochemicals or new materials.

Bioethanol for use in vehicles is becoming a substantial part of global energy infrastructure because it is renewable and some emissions are reduced. Carbon monoxide (CO) emissions and total hydrocarbons (THC) are reduced, but there is still controversy regarding emissions of nitrogen oxides (NOThe use of bioethanol can significantly reduce petroleum use and greenhouse gas emissions worldwide. Given the extent of its use, it is important to understand its effect on urban pollution. There is a controversy on whether there is a reduction or increase in PM emission when using ethanol blends. Primary emissions of THC, CO, CO

The synthesis of new methallyl-ferrocenyl-thiazoline-nickel complexes [1-(2-thiazolin-2-yl)-2-(R-thio)-ferrocene-κ2N,S]-(η3-methallyl)nickel(II) [Y] (1-3, R = Me, i-Pr, Ph, Y = BF4- 4, R = Me, Y = BAr´4-) by reaction with 2-ferrocenyl-2-thiazoline ligands L1–3 with [Ni-(η3-(CH2)2CMe)Cl]2 in presence of fluoroborate salts (Y = BAr´4-; BF4-) is reported. The complexes 1–4 were obtained in high yields, and characterized by 1H, 13C, 19F and 11B NMR, FTIR. The X-Ray diffraction analysis of 4 confirmed the formation of a single isomer containing a nickel center coordinated to L1 in a bidentate [N,S] fashion and to a η3-methallyl ligand. These complexes catalyzed efficiently the ethylene oligomerization when tris(pentafluorophenyl)borane (BCF) was used as co-activator. All catalytic precursors produced C4 and C6 fractions. Complex 1 showed higher activity with TOF 3006 h-1 at room temperature with selectivity of 86% to C4 fraction. In contrast, catalyst 2 was more selective to the formation of 1-butene, but with low activity. DFT-Computational studies of complex-BCF adducts show than these species behave as frustrated Lewis pairs, mainly stabilized by long-range interactions enhancing the acceptor character of the complexes. Structural modifications over the sulfanyl group tune the acceptor character of Ni center, affecting their catalytic performance.

We report the synthesis of a series of ferrocene amphiphilic donor–π–acceptor dyes, with the general formula (Fc-CHCH-HetNC16H33)+ X− [where: Fc behaves as the donor group, a double bond as the π bridge, and 2-,4-pyridinium and 4-quinolinium as the potent acceptor groups (2a–b and 4, X = Br− or BF4−)], in good overall yields. Together with their neutral counterparts (6a–b and 7), the photophysical and electrochemical properties of these compounds were investigated by means of UV-Vis spectroscopy and cyclic voltammetry. The optical and electrochemical band gaps of these dyes were calculated, which indicated that 4 has the lowest bandgap value. Time-dependent DFT calculations indicate that the lowest energy absorption band displayed for these compounds has mainly metal-to-ligand charge transfer character, with the HOMO–LUMO electronic transition being the main contribution.

A selective electromembrane extraction procedure for the extraction of Enrofloxacin, Marbofloxacin and Flumequine, usually employed as antibiotic in veterinarian use, is proposed by using a chitosan biofilm, composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336, as active biopolymeric support. The interaction mechanism occurring between the target drugs and the biopolymer has been deeply studied using the Quantum Theory of Atoms in Molecules. The obtained results show the interaction between the extracted fluoroquinolones and the biomembrane is stabilized by two hydrogen bonds formed between both the carboxyl and keto groups of the drugs with both the amine and hydroxyl groups of glucosamine in the biopolymer. The energetic results agree with the high extraction efficiency obtained for Marbofloxacin, Enrofloxacin and Flumequine in terms of enrichment factors (83, 82 and 58, respectively) in presence of other fluoroquinolones. Under optimum conditions, the proposed electromembrane extraction method exhibits wide linear ranges of 4.2–200 μg L−1, 5.6–200 μg L−1 and 5.1–200 μg L−1, respectively; low limits of detection close to 1.3 μg L−1 and appropriate repeatability (relative standard deviation values 4–7%).

Developing highly efficient photocatalysts for artificial photosynthesis is one of the grand challenges in solar energy conversion. Among advanced photoactive materials, conjugated porous polymers (CPPs) possess a powerful combination of high surface areas, intrinsic porosity, cross-linked nature, and fully π-conjugated electronic systems. Here, based on these fascinating properties, organic–inorganic hybrid heterostructures composed of CPPs and TiO2for the photocatalytic CO2reduction and H2evolution from water are developed. The study is focused on CPPs based on the boron dipyrromethene (BODIPY) and boron pyrrol hydrazine (BOPHY) families of compounds. It is shown that hybrid photocatalysts are active for the conversion of CO2mainly into CH4and CO, with CH4production 4 times over the benchmark TiO2. Hydrogen evolution from water surpassed by 37.9-times that of TiO2, reaching 200mmol gcat−1and photonic efficiency of 20.4% in the presence of Pt co-catalyst (1 wt% Pt). Advanced photophysical studies, based on time-resolved photoluminescence and transient absorption spectroscopy, reveal the creation of a type II heterojunction in the hybrids. The unique interfacial interaction between CPPs and TiO2results in longer carriers’ lifetimes and a higher driving force for electron transfer, opening the door to a new generation of photocatalysts for artificial photosynthesis.

The antioxidant and antimicrobial effects of Hierba Santa (Piper auritum Kunth) ethanolic extracts (HSEE) from plant powder of particle sizes 425 μm (EPA) and 850 μm (EPB) were evaluated in raw and raw-cooked beef burgers stored for 9 days at 4 °C, as well as raw-frozen and raw-frozen-cooked beef burgers stored for 90 days at −20 °C. Four treatments were prepared, including control (without extract), solution of sodium ascorbate (NaASC at 500 mg/kg), MEPA (meat with HSEE from EPA at 750 mg/kg) and MEPB (meat with HSEE from EPB at 750 mg/kg). The in vitro antioxidant and antimicrobial activities as well as total phenolic, chlorophyll and carotenoid content of HSEE were studied. The chemical composition was evaluated in beef used for the burgers. Beef burgers were evaluated for thiobarbituric acid reactive substances (TBARS), pH, color, metmyoglobin content and microbial load. Results indicated that HSEE showed in vitro antioxidant activity and their incorporation in beef burgers inhibited lipid oxidation compared with NaASC, while pH was lower than the maximum allowed limit. However, neither EPB nor EPA were effective in reducing the total bacteria count (TBC) in raw beef burgers. Therefore, HSEE could be recommended as a natural antioxidant in beef burgers.

Background and aims Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE (−/−) mice and the underlying molecular mechanisms. Methods and results WT and ApoE (−/−) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus 15 min before R; 4) ApoE (−/−) Control Group, receiving WFI; 5) ApoE (−/−) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE (−/−) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus, 15 min before R. Ischemic area/area at risk (I/R%) ratio was measured. Blood samples and ischemic myocardial tissue were collected at the 10th min of reperfusion for assessment of troponin I, malondialdehyde (MDA), nitrotyrosine (NT), p-eNOS, eNOS, p-Akt, Akt, p-p42/p-p44, p-GSK3β, GSK3β, IL-6, Nrf2, HO-1 and MnSOD expression. The effect of SFE on Nrf2 expression was also evaluated in vitro . SFE reduced infarct size in WT (16.15 ± 3.7% vs 41.57 ± 2.48%, ***p (−/−) mice (16.14 ± 1.47% vs 45.57 ± 1.73%, ***p (−/−) mice). Mice receiving SFE showed increased levels of eNOS, p-Akt, p-ERK1/2, p-44/p-42 and p-GSK3β-Ser9 and reduced expression of IL-6 and iNOS; furthermore, SFE reduced the levels of MDA and NT. SFE induced Nrf2 expression and its downstream targets, HO-1 and MnSOD in the myocardium of the treated animals, and induced Nrf2 expression in vitro in a dose-dependent manner. Conclusions SFE limits myocardial infarction in Wild-Type and ApoE (−/−) mice in a multifaceted manner including activation of Akt/eNOS/ERK1/2/GSK3-β and through Nrf2 pathway, bestowing antioxidant protection against I/R.

Saccharomyces cerevisiae is a model to understand basic aspects of protein glycosylation pathways. Although these metabolic routes have been thoroughly studied, there are still knowledge gaps; among them, the role of the MNT1/KRE2 gene family. This family is composed of nine members, with only six functionally characterized. The enzymes Ktr1, Ktr3, and Mnt1/Kre2 have overlapping activities in both O-linked and N-linked glycan synthesis; while Ktr2 and Yur1 participate exclusively in the elongation of the N-linked glycan outer chain. KTR6 encodes for a phosphomannosyltransferase that synthesizes the cell wall phosphomannan. Here, we aimed to establish the functional role of KTR4, KTR5 and KTR7 in the protein glycosylation pathways, by using heterologous complementation in Candida albicans null mutants lacking members of the MNT1/KRE2 gene family. The three S. cerevisiae genes restored defects in the C. albicans N-linked glycosylation pathway. KTR5 and KTR7 partially complemented a C. albicans null mutant with defects in the synthesis of O-linked glycans, and only KTR4 fully elongated the O-linked glycans like wild-type cells. Therefore, our results suggest that the three genes have a redundant activity in the S. cerevisiae N-linked glycosylation pathway, but KTR4 plays a major role in O-linked glycan synthesis.

A simple arylhydrazone-containing the benzothiazole moiety which may be used as efficient ligand in the palladium-catalyzed Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions, under infrared irradiation as an alternative source of energy, is presented. The reactions proceeded with extremely high efficiency under mild conditions and produced very good yields.

The synthesis and characterization of a new family of thiophene bridged bis-naphthalimides (2NDI-XT) are presented here. These semiconductors have been designed to have an even or an odd number of thiophene rings, with the aim of studying molecules with varying and alternant molecular dipolar moments, which are expected to significantly impact molecular packing. Following a theoretical analysis, the stability of a series of π-dimers showing either parallel or antiparallel packing dispositions has been predicted. Our results point out to a molecular packing motif in which both the NDI and oligothiophene fragments are cofacial for all the semiconductors investigated, regardless of their estimated molecular dipole moments. These, in principle, unexpected results are in good agreement with the field-effect mobilities measured in a bottom-gate top-contact transistor architecture, which show no straightforward correlation between device performance and dipolar moment. Ambipolar field-effect mobilities are recorded for the most extended π-systems, 5,5′-bis(2-hexyldecylbenzo[lmn]thieno[3′,4′:4,5]imidazo[2,1-b][3,8]phenanthroline-1,3,6(2H)-trione-10-yl)-2,2′-bithiophene, 2NDI-4T and 5,5′′-bis(2-hexyldecylbenzo[lmn]thieno[3′,4′:4,5]imidazo[2,1-b][3,8]phenanthroline-1,3,6(2H)-trione-10-yl)-2,2′:5′,2′′-terthiophene, 2NDI-5T, with the latter showing quite balanced electron and hole mobilities of 1.8 × 10−3 cm2 V−1 s−1 and 8.4 × 10−3 cm2 V−1 s−1, respectively.

Neuronal hippocampal death can be induced by exacerbated levels of cortisol, a condition usually observed in patients with Major depressive disorder (MDD). Previous in vitro and in vivo studies showed that ursolic acid (UA) elicits antidepressant and neuroprotective properties. However, the protective effects of UA against glucocorticoid-induced cytotoxicity have never been addressed. Using an in vitro model of hippocampal cellular death induced by elevated levels of corticosterone, we investigated if UA prevents corticosterone-induced cytotoxicity in HT22 mouse hippocampal derived cells. Concentrations lower than 25 µM UA did not alter cell viability. Co-incubation with UA for 48 h was able to protect HT22 cells from the reduction on cell viability and from the increase in apoptotic cells induced by corticosterone. Inhibition of protein kinase A (PKA), protein kinase C (PKC) and, Ca2+/calmodulin-dependent protein kinase II (CaMKII), but not phosphoinositide 3-kinase(PI3K), by using the pharmacological the inhibitors: H-89, chelerythrine, KN-62, and LY294002, respectively totally abolished the cytoprotective effects of UA. Finally, UA abrogated the reduction in phospho-extracellular signal–regulated kinases 1 and 2 (ERK1/2) but not in phospho-c-Jun kinases induced by corticosterone. These results indicate that the protective effect of UA against the cytotoxicity induced by corticosterone in HT22 cells may involve PKA, PKC, CaMKII, and ERK1/2 activation. The cytoprotective potential of UA against corticosterone-induced cytotoxicity and its ability to modulate intracellular signaling pathways involved in cell proliferation and survival suggest that UA may be a relevant strategy to manage stress-related disorders such as MDD.

Mango (Mangifera indica L.) is an important commercial fruit that shows a noticeable loss of firmness during ripening. Polygalacturonase (PG, E.C. 3.2.1.15) is a crucial enzyme for cell wall loosening during fruit ripening since it solubilizes pectin and its activity correlates with fruit softening. Mango PGs were mapped to a genome draft using seventeen PGs found in mango transcriptomes and 48 bonafide PGs were identified. The phylogenetic analysis suggests that they are related to Citrus sinensis, which may indicate a recent evolutive divergence and related functions with orthologs in the tree. Gene expression analysis for nine PGs showed differential expression for them during postharvest fruit ripening, MiPG21-1, MiPG14, MiPG69-1, MiPG17, MiPG49, MiPG23-3, MiPG22-7 and MiPG16 were highly up-regulated. PG enzymatic activity also increased during maturation and these results correlate with the loss of firmness observed in mango during postharvest ripening, between the ethylene production burst and the climacteric peak. The analysis of PGs promoter regions identified regulatory sequences associated to ripening such as MADS-box, ethylene regulation like ethylene insensitive 3 (EIN3) factors, APETALA2-like and ethylene response element factors. During mango fruit ripening the action of at least these nine polygalacturonases contribute to softening, and their expression is regulated at the transcriptional level. The prediction of the tridimensional structure of some PGs showed a conserved parallel beta-helical fold related to polysaccharide hydrolysis and a modular architecture where exons correspond to structural elements. Further biotechnological approaches could target specific softening-related PGs to extend mango postharvest shelf life.

Nanoparticles of the poly(methyl methacrylate-co-methacrylic acid) or copolymer of P(MMA-co-MAA), were prepared by semicontinuous heterophase polymerization; they show a mean diameter of 12 nm and a 1.75 MMA/MAA molar ratio determined by carbon-13 nuclear magnetic resonance. The content of MAA, greater than that of Eudragit S100, copolymer of P(MMA-co-MAA) accepted by the FDA for the preparation of tablets, ensures its biocompatibility and its metabolism without toxic effects. Loaded with up to 22 wt. % aspirin, that is, acetylsalicylic acid (ASA), these nanoparticles increase slightly their size, according to transmission electron microscopy; however, the presence of ASA on the nanoparticle surface decreases their stability, which leads to a certain aggregation of the particles in the dispersion. Fourier transform infrared spectrometry was used for demonstrating the loading of ASA in the nanoparticles.

Wastewaters from some industries contain high levels of nitrate but an insufficient amount of electron donor to sustainbiological denitrification. An option...

Mesquite (Prosopis sp) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E2) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E2; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E2. The main disruptor of sexual behavior was E2, however after 40 and 50 days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E2. The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in leucaena extract and E2 groups, but not in mesquite- and phytoestrogens- treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E2 treated males. These results suggest that mesquite pod and Leucaena extracts cause effects similar to those of phytoestrogens in male rat reproduction, these effects were lower than those caused by E2.

Maple syrup is a natural sweetener obtained from the sap of maple trees (Acer saccharum), highly rich in bioactive molecules placing it among the most desirable and natural sweeteners for human consumption (agave, sugarcane, corn and honey). Carbohydrate profiles (amounts and composition) as well as FTIR-PCA classification of maple syrup were performed and compared to other natural sweeteners. TLC and HPAEC-PAD revealed that maple syrup exhibits unique carbohydrate profiles dominated by high sucrose content (511–688 mg/g) followed by glucose and fructose traces. Alternately and highly relevant, it was possible to identify three oligosaccharides, not previously reported in maple syrup, with potential to be used as authenticity markers. The FTIR spectra displayed the most characteristic differences in the carbohydrate region (1185–950 cm−1), particularly, maple syrup exhibited strong absorption bands at 997 and 1054 cm−1 wavelengths in agreement with their high sucrose content. Principal component analysis of the FTIR carbohydrates region allowed maple syrup to be distinguished from other natural sweeteners based on botanical source. The above information would be helpful for the authentication, characterization, and subsequent detection of intentional adulteration of this natural sweetener.

Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day (p.o.) and corticosterone for 21 days and the daily administrations of experimental drugs were given immediately prior to corticosterone (20 mg/kg/day, p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (−/−)) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle. Twenty-four hours after the last treatments, the behavioral tests and biochemical assays were performed. Agmatine treatment for 21 days was able to abolish the corticosterone-induced depressive-like behavior and the alterations in the immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and glutamate levels. Agmatine also abolished the corticosterone-induced changes in the morphology of astrocytes and microglia in CA1 region of hippocampus. In addition, agmatine treatment in control mice increased noradrenaline, serotonin, and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine’s ability to produce an antidepressant-like effect was abolished in Nrf2 (−/−) mice. The present results reinforce the participation of Nrf2 in the antidepressant-like effect produced by agmatine and expand literature data concerning its mechanisms of action., This work was supported by CNPq, CAPES/PDSE, CAPES/PROCAD, Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC) Project/ PRONEX Program CNPq/FAPESC (Brazil) to ALSR. The 8th Convocatoria de proyectos de Cooperación Interuniversitaria UAM-Santander con America Latina, Spanish Ministry of Economy and Competence Ref. SAF2012-32223 to MGL and ALSR. This work was also supported by FIS CA12/00122 to ARN and FPU12/02220 to AW.

Ibuprofen-loaded polymeric particles with around 9.2 nm in mean diameter, as determined by electron microscopy, dispersed in an aqueous media containing up to 12.8% solids were prepared by semicontinuous heterophase polymerization. The polymeric material is a (2/1 mol/mol) methyl methacrylate-co-methacrylic acid copolymer similar to Eudragit S100, deemed safe for human consumption and used in the manufacturing of drug-loaded pills as well as micro- and nanoparticles. The loading efficiency was 100%, attaining around 10-12% in drug content. Release studies showed that the drug is released from the nanoparticles at a slower rate than that in the case of free IB. Given their size as well as the pH values required for their dissolution, it is believed that this type of particles could be used as a basis for preparing nanosystems loaded with a variety of drugs.

Ultrafine nanoparticles, less than 10 nm in mean diameter, of the FDA approved copolymer methyl methacrylate- (MMA-)co-methacrylic acid (MAA), 2/1 (mol/mol), were prepared. The method used for the preparation of these particles stabilized in a latex containing around 11% solids includes the dosing of the monomers mixture on a micellar solution preserving monomer starved conditions. It is thought that the operation at these conditions combined with the hydrophilicity of MMA and MAA units favors the formation of ultrafine particles; the propagation reaction carried out within so small compartments renders copolymer chains rich in syndiotactic units very likely as consequence of the restricted movements of the end propagation of the chains. Because of their biocompatibility and biodegradability as well as their extremely small size these nanoparticles could be used as vehicles for improved drug delivery in the treatment of chronic-degenerative diseases.

The objective of this study was to determine the effect of supplemented prebiotics: inulin (I), oligofructose (O), agave fructans (A) and their mixtures in three levels, 20, 40 and 60 g prebiotics/kg puree on the physicochemical and sensorial properties of a dehydrated apple matrix (DAM), fruit leather type. A simplex-centroid design was used to formulate the different mixtures. After that, fructans were identified in the matrices using thin-layer chromatography and high-performance anion-exchange chromatography with pulsed amperometric detection and enzymatic kits. A descriptive quantitative method was used to determine sensory profile of the matrices. The sensory acceptability was measured by a 7-point hedonic scale. Matrices supplemented with solely A and O, were significantly smoother and more qualified in acceptability compared to the control. The behavior of DAM with inulin was different; it increased hardness and decreased acceptability. In general, mixtures of prebiotics had a synergistic effect on matrices hardness. The optimum formulation corresponded to the DAM supplemented with agave fructans, indicating that it is possible to obtain a fruit leather type product with prebiotic potential.

We describe the synthetic application of a family of selenoamides [R–C(Se)NHCH2R’ (R = Fc, Aryl, Het, alkyl) tethered to N-heterocyclic motifs (R’ = 2-pyridyl and 2-thiazolyl) obtained from their corresponding Fischer ethoxy carbene complexes [R–C(Cr(CO)5)OEt] using a tandem procedure that involves an aminolysis/seleniurative demetallation. The selenoamides obtained are used as accessible building-block to easily obtain a two-ring fused system with a bridge-head nitrogen atom. This study reveals that C Se bond can be readily and speedily activated with iodine at room temperature, in grinding conditions, for obtaining a family of imidazo[1,5-a]pyridines in good to excellent yields in only 1 min of reaction time. This methodology was successfully extended to the synthesis of ferrocenyl imidazo[1,5-b]thiazole in excellent yield.

The development of a new method for covalent immobilization of biomolecules on the surface of bare gold nanoparticles (AuNPs) by using crosslinking agents in one step is presented. A very compatible biopolymer such as chitosan has been used as a target molecule to probe the viability of the proposed methodology. Click chemistry, based on biocompatible reactions and coupling with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide allow to analyze the covalent interactions between the metal nanoparticles and the biopolymer. Spectra deconvolution technique and Zeta potential measurements confirm the covalent interaction. The present study allows to quantify the proportion of AuNPs covalently adhered to the chitosan, which depends on the solution pH. The obtained results indicates that covalent interactions can be increased up to 25% in relation to total system interactions, which are mostly electrostatic. The proposed strategy opens up a new pathway for biomedical applications because the control of the chemical linkage can be directly performed on the nanoparticle surface without using any molecular intermediate, which may improve the encapsulation efficiency on drug delivery therapies.