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1.
Food Res Int ; 194: 114938, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232548

ABSTRACT

The aroma is critical in the reproductive biology of truffles and in their commercial quality. However, previous research has almost exclusively focused on characterizing ripe ascocarps. We characterized the volatilome of the highly-prized black truffle (Tuber melanosporum) ascocarps from July, in an early development stage, to March, in the late harvesting season, and investigated the relationships among aroma, ascocarp growth and morphogenetic development. The aroma profile was analyzed using a head space gas chromatography technique coupled with mass spectrometer. Seventy-one volatile compounds were identified and three development stages were clearly distinguished according to the volatile profile. In unripe ascocarps of July-September, the profile was dominated by methanethiol (19 %), 4-penten-2-ol (11 %) and acetone (11 %), the monthly mean weight of ascocarps ranged 2-20 g, and morphogenetic stages 4-6a were prevalent. In unripe ascocarps of October-December, the most abundant volatiles were 4-penten-2-ol (21 %), methanethiol (20 %) and ethanol (13 %), the monthly mean ascocarp weight ranged 28-43 g, and morphogenetic stages 6a, 6b-c were prevalent. In ripe ascocarps (December-March), the most abundant volatiles were 4-penten-2-ol (17 %), dimethyl sulfide (16 %) and ethanol (10 %), ascocarp weight did not increase significantly, and 6b-c was practically the sole morphogenetic stage. Thirty volatiles were associated to one of these three development stages. Amongst those with higher occurrence, 4-penten-2-ol, dimethyl sulfide, ethyl acetate, 2-pentanol and 2-butanone were associated to ripe truffles, whereas methanethiol, isobutyl isobutyrate, butanedione and 3-methylanisole were associated to unripe truffles.


Subject(s)
Ascomycota , Gas Chromatography-Mass Spectrometry , Odorants , Volatile Organic Compounds , Volatile Organic Compounds/analysis , Odorants/analysis , Ascomycota/growth & development , Ascomycota/metabolism , Fruiting Bodies, Fungal/growth & development , Fruiting Bodies, Fungal/chemistry , Seasons
2.
Org Biomol Chem ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263821

ABSTRACT

The [3 + 2] annulation reaction between a thiourea, an ambident dinucleophile, and a 2-(phenacylethylidene)cyclobutanone, containing a novel pull-pull alkene system, could in principle proceed with several chemo- and regioselectivity profiles. Here we describe a convenient synthesis of the functionalized cyclobutanone substrates and show that they react with thioureas in a manner that is rationalized mechanistically in terms of the steric and electronic effects at play. The [3 + 2] annulation proceeds in mild, additive-free conditions to provide access to previously unknown cyclobutane-fused imidazolidine-2-thione and thiazolidine-2-imine derivatives in good yields.

3.
Foods ; 13(17)2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39272569

ABSTRACT

Extracts from locally grown aromatic plants can enhance the geographical characteristics and microbial stability of craft beers, which are often not pasteurized or filtered. Here, the chemical and antimicrobial properties of aqueous extracts from leaves of Myrtus communis L., Pistacia lentiscus L., Artemisia arborescens L., and floral wastes of Crocus sativus L., all cultivated in Sardinia (Italy), were assessed. P. lentiscus extract had the highest polyphenol content (111.20 mg GAE/g), followed by M. communis (56.80 mg GAE/g), C. sativus (32.80 mg GAE/g), and A. arborescens (8.80 mg GAE/g). Notably, only the M. communis extract demonstrated significant inhibitory activity against pathogenic and spoilage microorganisms, with minimum inhibitory concentrations of 0.18, 0.71, and 1.42 mg GAE/mL against Staphylococcus aureus, Lactiplantibacillus plantarum, and Lacticaseibacillus casei, respectively. Additionally, it reduced the growth of Levilactobacillus brevis and Fructilactobacillus lindneri at concentrations of 0.35 and 0.71 mg GAE/mL, respectively. Based on its significant antimicrobial activity, the M. communis extract was further characterized using high-resolution mass spectrometry, revealing high abundances of nonprenylated phloroglucinols, flavonoid derivatives (myricetin), and quinic acids. Lastly, adding M. communis extract (2.84 mg GAE/mL) to commercial beer effectively prevented the growth of L. brevis and F. lindneri, showing its potential to avoid beer's microbial spoilage.

4.
Food Chem ; 461: 140850, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39173257

ABSTRACT

Lipid hydrolysis process during IF digestion, particularly the characterization of the lipidome and the resulting lipid breakdown products, has not been thoroughly investigated. This study aimed to compare the lipid hydrolysis profiles during the in vitro dynamic digestion of IFs made from whole sheep and goat milk. Using a lipidomics platform and multivariate statistical analysis, we observed changes in complex lipid levels during digestion. In the gastric compartment, we noted a progressive hydrolysis of triacylglycerols, phosphatidylcholines, and sphingomyelins. Conversely, lipolysis breakdown products like monoacylglycerols (e.g., MG(16:0), MG(18:0)), diacylglycerols, lysophosphatidylcholines (LPC 16:0, LPC 18:1, LPC 18:2), and free fatty acids increased in the intestinal compartment. The lipolysis trends were similar for both types of infant formulas, with long-chain fatty acid triglycerides (C > 46) exhibiting lower digestibility compared to medium-chain fatty acid triglycerides. Overall, these results indicate that sheep milk can be used as an ingredient in the manufacturing of IF.


Subject(s)
Digestion , Goats , Infant Formula , Lipidomics , Milk , Animals , Goats/metabolism , Milk/chemistry , Milk/metabolism , Sheep/metabolism , Infant Formula/chemistry , Infant Formula/analysis , Humans , Infant , Triglycerides/metabolism , Triglycerides/chemistry , Triglycerides/analysis , Models, Biological , Lipids/chemistry , Lipids/analysis
5.
Life Sci Space Res (Amst) ; 42: 108-116, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39067982

ABSTRACT

Long-term spatial missions will require sustainable methods for biomass production using locally available resources. This study investigates the feasibility of cultivating Chlorella vulgaris, a high value microalgal specie, using a leachate of Martian regolith and synthetic human urine as nutrient sources. The microalga was grown in a standard medium (BBM) mixed with 0, 20, 40, 60, or 100 % Martian medium (MM). MM did not significantly affect final biomass concentrations. Total carbohydrate and protein contents decreased with increasing MM fractions between 0 % and 60 %, but biomass in the 100% MM showed the highest levels of carbohydrates and proteins (25.2 ± 0.9 % and 37.1 ± 1.4 % of the dry weight, respectively, against 19.0 ± 1.7 % and 32.0 ± 2.7 % in the absence of MM). In all MM-containing media, the fraction of the biomass represented by total lipids was lower (by 3.2 to 4.5%) when compared to BBM. Conversely, total carotenoids increased, with the highest value (97.3 ± 1.5 mg/100 g) measured with 20% MM. In a three-dimensional principal component analysis of triacylglycerols, samples clustered according to growth media; a strong impact of growth media on triacylglycerol profiles was observed. Overall, our findings suggest that microalgal biomass produced using regolith and urine can be used as a valuable component of astronauts' diet during missions to Mars.


Subject(s)
Chlorella vulgaris , Mars , Chlorella vulgaris/chemistry , Chlorella vulgaris/growth & development , Urine/chemistry , Culture Media , Biomass , Proteins/analysis , Lipids/analysis , Carbohydrates/analysis , Carotenoids/analysis , Minerals/analysis , Triglycerides/analysis , Space Research
6.
Food Chem ; 456: 139930, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38876075

ABSTRACT

The effect of different sub-pasteurization heat treatments and different ripening times was investigated in this work. The metabolite profiles of 95 cheese samples were analyzed using GC-MS in order to determine the effects of thermal treatment (raw milk, 57 °C and 68 °C milk thermization) and ripening time (105 and 180 days). ANOVA test on GC-MS peaks complemented with false discovery rate correction was employed to identify the compounds whose levels significantly varied over different ripening times and thermal treatments. The univariate t-test classifier and Partial Least Square Discriminant Analysis (PLS-DA) provided acceptable classification results, with an overall accuracy in cross-validation of 76% for the univariate model and 72% from the PLS-DA. The metabolites that mostly changed with ripening time were amino acids and one endocannabinoid (i.e., arachidonoyl amide), while compounds belonging to the classes of biogenic amines and saccharides resulted in being strongly affected by the thermization process.


Subject(s)
Cheese , Gas Chromatography-Mass Spectrometry , Hot Temperature , Metabolomics , Cheese/analysis , Animals , Discriminant Analysis , Milk/chemistry , Milk/metabolism , Food Handling , Amino Acids/analysis , Amino Acids/metabolism , Amino Acids/chemistry , Cattle
7.
Food Chem ; 449: 139165, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38574520

ABSTRACT

Microalgae are considered as a potential source of bioactive compounds to be used in different fields including food and pharmaceutical industry. In this context, fatty acid esters of hydroxy-fatty acids (FAHFA) are emerging as a new class of compounds with anti-inflammatory and anti-diabetic properties. An existing gap in the field of algal research is the limited knowledge regarding the production of these compounds. Our research questions aimed to determine whether the microalga H. pluvialis can synthesize FAHFA and whether the production levels of these compounds are increased when cultivated in a CO2-rich environment. To answer these questions, we used a LC-QTOF/MS method for the characterization of FAHFA produced by H. pluvialis while an LC-MS/MS method was used for their quantitation. The cultivation conditions of H. pluvialis, which include the utilization of CO2, can result in a 10-50-fold increase in FAHFA production.


Subject(s)
Carbon Dioxide , Fatty Acids , Microalgae , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Microalgae/chemistry , Microalgae/metabolism , Microalgae/growth & development , Fatty Acids/chemistry , Fatty Acids/metabolism , Tandem Mass Spectrometry , Chlorophyta/chemistry , Chlorophyta/growth & development , Chlorophyta/metabolism
8.
Poult Sci ; 103(5): 103616, 2024 May.
Article in English | MEDLINE | ID: mdl-38503138

ABSTRACT

Eggs, as a crucial source of essential nutrients for consumers, possess a high nutritional value owing to their rich composition of vital components essential for human health. While previous research has extensively investigated genetic factors influencing egg quality, there has been a limited focus on exploring the impact of specific strains, particularly within the African context, on the polar metabolite profile of eggs. In this extensive study, we conducted an untargeted analysis of the chemical composition of both albumen and yolk from 3 distinct strains of hens-Blue Holland, Sasso, and Wassache-raised under identical feeding conditions. Utilizing gas chromatography coupled with mass spectrometry (GC-MS), we meticulously examined amino acids, carbohydrates, fatty acids, and other small polar metabolites. In total, 38 and 44 metabolites were identified in the whites and yolk, respectively, of the 3 studied strains. The application of chemometric analysis revealed notable differences in metabolite profiles with 8 relevant metabolites in each egg part. These metabolites include amino acids (N-α-Acetyl-L-lysine, lysine, L-valine, L-Tryptophan), fatty acids (oleic acid, linoleic acid, palmitic acid and stearic acid), and carbohydrates (d-glucose, maltose, lactose). These findings shed light on strain-specific metabolic nuances within eggs, emphasizing potential nutritional implications. The ensuing discussion delves into the diverse metabolic pathways influenced by the identified metabolites, offering insights that contribute to a broader understanding of egg composition and its significance in tailoring nutritional strategies for diverse populations.


Subject(s)
Chickens , Gas Chromatography-Mass Spectrometry , Animals , Chickens/genetics , Chickens/metabolism , Gas Chromatography-Mass Spectrometry/veterinary , Metabolomics , Eggs/analysis , Metabolome , Egg Yolk/chemistry , Female , Fatty Acids/metabolism , Fatty Acids/analysis , Fatty Acids/chemistry , Amino Acids/metabolism , Amino Acids/analysis , Ovum/chemistry
9.
Life (Basel) ; 14(2)2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38398760

ABSTRACT

The cultivation of cyanobacteria by exploiting available in situ resources represents a possible way to supply food and oxygen to astronauts during long-term crewed missions on Mars. Here, we evaluated the possibility of cultivating the extremophile cyanobacterium Chroococcidiopsis thermalis CCALA 050 under operating conditions that should occur within a dome hosting a recently patented process to produce nutrients and oxygen on Mars. The medium adopted to cultivate this cyanobacterium, named Martian medium, was obtained using a mixture of regolith leachate and astronauts' urine simulants that would be available in situ resources whose exploitation could reduce the mission payload. The results demonstrated that C. thermalis can grow in such a medium. For producing high biomass, the best medium consisted of specific percentages (40%vol) of Martian medium and a standard medium (60%vol). Biomass produced in such a medium exhibits excellent antioxidant properties and contains significant amounts of pigments. Lipidomic analysis demonstrated that biomass contains strategic lipid classes able to help the astronauts facing the oxidative stress and inflammatory phenomena taking place on Mars. These characteristics suggest that this strain could serve as a valuable nutritional resource for astronauts.

10.
Molecules ; 28(18)2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37764476

ABSTRACT

The spread of Human Immunodeficiency Virus (HIV) still represents a global public health issue of major concern, and would benefit from unveiling unique viral features as targets for drug design. In this respect, HIV-1 integrase (IN), due to the absence of homologs in human cells, is a popular target for the synthesis of novel selective compounds. Moreover, as drug-resistant viral strains are rapidly evolving, the development of novel allosteric inhibitors is acutely required. Recently, we have observed that Kuwanon-L, quinazolinones and thienopyrimidinones containing at least one polyphenol unit, effectively inhibited HIV-1 IN activity. Thus, in the present research, novel dihydroxyphenyl-based thienopyrimidinone derivatives were investigated for their LEDGF/p75-dependent IN inhibitory activity. Our findings indicated a close correlation between the position of the OH group on the phenyl moiety and IN inhibitory activity of these compounds. As catechol may be involved in cytotoxicity, its replacement by other aromatic scaffolds was also exploited. As a result, compounds 21-23, 25 and 26 with enhanced IN inhibitory activity provided good lead candidates, with 25 being the most selective for IN. Lastly, UV spectrometric experiments suggested a plausible allosteric mode of action, as none of the thienopirimidinones showed Mg2+ chelation properties otherwise typical of IN strand transfer inhibitors (INSTIs).

11.
Arch Pharm (Weinheim) ; 356(9): e2300256, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37452407

ABSTRACT

The increasing misuse of novel synthetic opioids (NSOs) represents a serious public health concern. In this regard, U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide) and related "U-compounds" emerged on recreational drug markets as synthetic substitutes for illicit heroin and constituents of counterfeit pain medications. While the pharmacology of U-compounds has been investigated using in vitro and in vivo methods, there is still a lack of understanding about the details of ligand-receptor interactions at the molecular level. To this end, we have developed a molecular modeling protocol based on docking and molecular dynamics simulations to assess the nature of ligand-receptor interactions for U-47700, N,N-didesmethyl U-47700, and U-50488 at the mu-opioid receptor (MOR) and kappa-opioid receptor (KOR). The evaluation of ligand-receptor and ligand-receptor-membrane interaction energies enabled the identification of subtle conformational shifts in the receptors induced by ligand binding. Interestingly, the removal of two key methyl groups from U-47700, to form N,N-didesmethyl U-47700, caused a loss of hydrogen bond contact with tryptophan (Trp)229, which may underlie the lower interaction energy and reduced MOR affinity for the compound. Taken together, our results are consistent with the reported biological findings for U-compounds and provide a molecular basis for the MOR selectivity of U-47700 and KOR selectivity of U-50488.


Subject(s)
Receptors, Opioid, kappa , Receptors, Opioid, mu , Receptors, Opioid, kappa/chemistry , Receptors, Opioid, kappa/metabolism , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology , Ligands , Structure-Activity Relationship , Receptors, Opioid, mu/metabolism , Analgesics, Opioid/pharmacology , Analgesics, Opioid/chemistry
12.
Metabolites ; 13(7)2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37512584

ABSTRACT

Seasonal variation in fatty acids and minerals concentrations was investigated through the analysis of Pecorino Romano cheese samples collected in January, April, and June. A fraction of samples contained missing values in their fatty acid profiles. Probabilistic principal component analysis, coupled with Linear Discriminant Analysis, was employed to classify cheese samples on a production season basis while accounting for missing data and quantifying the missing fatty acid concentrations for the samples in which they were absent. The levels of rumenic acid, vaccenic acid, and omega-3 compounds were positively correlated with the spring season, while the length of the saturated fatty acids increased throughout the production seasons. Concerning the classification performances, the optimal number of principal components (i.e., 5) achieved an accuracy in cross-validation equal to 98%. Then, when the model was tasked with imputing the lacking fatty acid concentration values, the optimal number of principal components resulted in an R2 value in cross-validation of 99.53%.

13.
Int J Mol Sci ; 24(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36901810

ABSTRACT

Lipidomics and metabolomics are nowadays widely used to provide promising insights into the pathophysiology of cellular stress disorders. Our study expands, with the use of a hyphenated ion mobility mass spectrometric platform, the understanding of the cellular processes and stress due to microgravity. By lipid profiling of human erythrocytes, we annotated complex lipids such as oxidized phosphocholines, phosphocholines bearing arachidonic in their moiety, as well as sphingomyelins and hexosyl ceramides associated with microgravity conditions. Overall, our findings give an insight into the molecular alterations and identify erythrocyte lipidomics signatures associated with microgravity conditions. If the present results are confirmed in future studies, they may help to develop suitable treatments for astronauts after return to Earth.


Subject(s)
Lipidomics , Weightlessness , Humans , Lipidomics/methods , Metabolomics , Sphingomyelins , Erythrocytes
14.
ACS Omega ; 8(2): 1957-1966, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36687088

ABSTRACT

Gibberellin derivatives are a family of tetracyclic diterpenoid plant hormones used in agriculture as plant growth regulators included in the European Directive 91/414. In the pesticide peer review process and to assess their toxicological relevance and product chemical equivalence, the European Food Safety Authority (EFSA) highlighted data gaps such as the identification of hydrolysis products and unknown impurities. The aspect of impurity characterization and quantitation is challenging and requires the use of hyphenated analytical techniques. In this regard, we used an LC-QTOF/MS and NMR analysis for the characterization of gibberellic acid impurities found in technical products. Gibberellic acid impurities such as gibberellin A1 (GA 1 ), 3-isolactone gibberellic acid (iso-GA 3 ), gibberellenic acid, 1α,2α-epoxygibberellin A3 (2-epoxy- GA 3 ), and (1α,2ß,3α,4bß,10ß)-2,3,7-trihydroxy-1-methyl-8-methylenegibb-4-ene-1,10-dicarboxylic acid were identified and successfully characterized. Moreover, an in silico investigation on selected gibberellic acid impurities and derivatives and their interactions with a gibberellin insensitive dwarf1 (GID1) receptor has been carried out by means of induced fit docking (IFD), generalized-Born surface area (MM-GBSA), and metadynamics (MTD) experiments. A direct HPLC method with DAD and MS for the detection of gibberellic acid and its impurities in a technical sample has been developed. Moreover, by means of the in silico characterization of the GID1 receptor-binding pocket, we investigated the receptor affinity of the selected gibberellins, identifying compounds (2) and (4) as the most promising hit to lead compounds.

15.
Biomedicines ; 10(12)2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36551863

ABSTRACT

BACKGROUND: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. METHODS: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. RESULTS: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. CONCLUSIONS: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.

16.
Sci Rep ; 12(1): 21923, 2022 12 19.
Article in English | MEDLINE | ID: mdl-36535959

ABSTRACT

Fibromyalgia (FM) is a chronic and systemic condition that causes widespread chronic pain, asthenia, and muscle stiffness, as well as in some cases depression, anxiety, and disorders of the autonomic system. The exact causes that lead to the development of FM are still unknown today. In a percentage of individuals, the symptoms of FM are often triggered and/or exacerbated by proximity to electrical and electromagnetic devices. Plasma metabolomic profile of 54 patients with fibromyalgia and self-reported electromagnetic sensitivity (IEI-EMF) were compared to 23 healthy subjects using gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis techniques. Before the GC-MS analysis the plasma samples were extracted with a modified Folch method and then derivatized with methoxamine hydrochloride in pyridine solution and N-trimethylsilyltrifuoroacetamide. The combined analysis allowed to identify a metabolomic profile able of distinguishing IEI-EMF patients and healthy subjects. IEI-EMF patients were therefore characterized by the alteration of 19 metabolites involved in different metabolic pathways such as energy metabolism, muscle, and pathways related to oxidative stress defense and chronic pain. The results obtained in this study complete the metabolomic "picture" previously investigated on the same cohort of IEI-EMF patients with 1H-NMR spectroscopy, placing a further piece for better understanding the pathophysiological mechanisms in patients with IEI-EMF.


Subject(s)
Chronic Pain , Fibromyalgia , Multiple Chemical Sensitivity , Humans , Gas Chromatography-Mass Spectrometry , Multiple Chemical Sensitivity/diagnosis , Multiple Chemical Sensitivity/etiology , Electromagnetic Fields , Fibromyalgia/complications , Metabolomics , Chronic Pain/complications
17.
Front Pharmacol ; 13: 935784, 2022.
Article in English | MEDLINE | ID: mdl-36059998

ABSTRACT

Grape pomaces have recently received great attention for their richness in polyphenols, compounds known to exert anti-inflammatory and antioxidant effects. These pomaces, however, have low brain bioavailability when administered orally due to their extensive degradation in the gastrointestinal tract. To overcome this problem, Nasco pomace extract was incorporated into a novel nanovesicle system called nutriosomes, composed of phospholipids (S75) and water-soluble maltodextrin (Nutriose® FM06). Nutriosomes were small, homogeneously dispersed, had negative zeta potential, and were biocompatible with intestinal epithelial cells (Caco-2). Nasco pomace extract resulted rich in antioxidant polyphenols (gallic acid, catechin, epicatechin, procyanidin B2, and quercetin). To investigate the neuroprotective effect of Nasco pomace in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), Nasco nutriosomes or Nasco suspension was administered intragastrically and their neuroprotective effects were evaluated. Degeneration of nigro-striatal dopaminergic neurons induced by subacute MPTP treatment, the pathological hallmark of PD, was assessed through immunohistochemical evaluation of tyrosine hydroxylase (TH) in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc), and the dopamine transporter (DAT) in CPu. Immunohistochemical analysis revealed that Nasco nutriosomes significantly prevented the reduction in TH- and DAT-positive fibres in CPu, and the number of TH-positive cells in SNc following subacute MPTP treatment, while Nasco suspension counteracted MPTP toxicity exclusively in SNc. Overall, these results highlight the therapeutic effects of Nasco pomace extract when administered in a nutriosome formulation in the subacute MPTP mouse model of PD and validate the effectiveness of the nutriosome preparation over suspension as an innovative nano-drug delivery system for in vivo administration.

18.
Sci Transl Med ; 14(649): eabl8503, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35704597

ABSTRACT

Cyclic GMP-phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (-3.40°, -5.96; -0.84, P = 0.011) and fiber shortening (-1.19%, -2.24; -0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14++CD16- monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications.


Subject(s)
Diabetes Mellitus, Type 2 , Erectile Dysfunction , MicroRNAs , Carbolines/pharmacology , Carbolines/therapeutic use , Cyclic Nucleotide Phosphodiesterases, Type 5 , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Double-Blind Method , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Female , Humans , Kinetics , Male , Penile Erection , Phosphodiesterase 5 Inhibitors/pharmacology , Phosphodiesterase 5 Inhibitors/therapeutic use , Tadalafil/pharmacology , Tadalafil/therapeutic use , Treatment Outcome , Ventricular Remodeling
19.
Int J Mol Sci ; 23(12)2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35743319

ABSTRACT

Erythrocytes are highly specialized cells in human body, and their main function is to ensure the gas exchanges, O2 and CO2, within the body. The exposure to microgravity environment leads to several health risks such as those affecting red blood cells. In this work, we investigated the changes that occur in the structure and function of red blood cells under simulated microgravity, compared to terrestrial conditions, at different time points using biochemical and biophysical techniques. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an augmentation in malondialdehyde (MDA) at increasing times. Moreover, experiments were performed to evaluate the lipid profile of erythrocyte membranes which showed an upregulation in the following membrane phosphocholines (PC): PC16:0_16:0, PC 33:5, PC18:2_18:2, PC 15:1_20:4 and SM d42:1. Thus, remarkable changes in erythrocyte cytoskeletal architecture and membrane stiffness due to oxidative damage have been found under microgravity conditions, in addition to factors that contribute to the plasticity of the red blood cells (RBCs) including shape, size, cell viscosity and membrane rigidity. This study represents our first investigation into the effects of microgravity on erythrocytes and will be followed by other experiments towards understanding the behaviour of different human cell types in microgravity.


Subject(s)
Weightlessness , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Glutathione/metabolism , Humans , Malondialdehyde/metabolism , Oxidative Stress
20.
Environ Sci Pollut Res Int ; 29(20): 29358-29367, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34988809

ABSTRACT

The insecticide 14C-chlorpyrifos was found mineralized in a Tunisian soil with repeated exposure to it. From this soil, a bacterial strain was isolated that was able to grow in a minimal salt medium (MSM) supplemented with 25 mg L-1 of chlorpyrifos. It was characterized as Serratia rubidaea strain ABS 10 using morphological and biochemical analyses, as well as 16S rRNA sequencing. In a liquid culture, the S. rubidaea strain ABS 10 was able to dissipate chlorpyrifos almost entirely within 48 h of incubation. Although the S. rubidaea strain ABS 10 was able to grow in an MSM supplemented with chlorpyrifos and dissipate it in a liquid culture, it was not able to mineralize 14C-chlorpyrifos. Therefore, it can be concluded that the dissipation capability of this bacteria might be attributed to its capacity to adsorb CHL. It can also be ascribed to other reasons such as the formation of biogenic non-extractable residues. In both non-sterile and sterile soil inoculated with S. rubidaea strain ABS 10, chlorpyrifos was more rapidly dissipated than in controls with DT50 of 1.38 and 1.05 days, respectively.


Subject(s)
Chlorpyrifos , Biodegradation, Environmental , Chlorpyrifos/analysis , RNA, Ribosomal, 16S , Serratia , Soil
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