Search

This study focuses on countering Fusarium graminearum , a harmful fungal pathogen impacting cereal crops and human health through mycotoxin production. These mycotoxins, categorized as type B trichothecenes, pose significant health risks. Research explores natural alternatives to synthetic fungicides, particularly investigating phenolics in grapevine byproducts. Thirteen eco-extracts from five French grape varieties (Merlot, Cabernet Sauvignon, Sauvignon blanc, Tannat, and Artaban) exhibited substantial antifungal properties, with ten extracts displaying remarkable effects. Extracts from grapevine stems and roots notably reduced fungal growth by over 91% after five days. Through UHPLC-HRMS/MS analysis and metabolomics, the study identified potent antifungal compounds such as ampelopsin A and cyphostemmin B, among other oligomeric stilbenes. Interestingly, this approach showed that flavan-3-ols have been identified as markers for extracts that induce fungal growth. Root extracts from rootstocks, rich in oligostilbenes, demonstrated the highest antifungal activity. This research underscores grapevine byproducts' potential both as a sustainable approach to control F. graminearum and mycotoxin contamination in cereal crops and the presence of different metabolites from the cultivars of grapevine, suggesting different activities.

Invasive plants efficiently colonize non-native territories, suggesting a great production of bioactive metabolites which could be effective antibiofilm weapons. Our study aimed to look for original molecules able to inhibit bispecies biofilm formed by S. aureus and C. albicans. Extracts from five invasive macrophytes (Ludwigia peploides, Ludwigia grandiflora, Myriophyllum aquaticum, Lagarosiphon major and Egeria densa) were prepared and tested in vitro against 24 h old bispecies biofilms using a crystal violet staining (CVS) assay. The activities of the extracts reducing the biofilm total biomass by 50% or more were comparatively analyzed against each microbial species forming the biofilm by flow cytometry (FCM) and scanning electron microscopy. Extracts active against both species were fractionated. Obtained fractions were analyzed by UHPLC-MS/MS and evaluated by the CVS assay. Chemical and biological data were combined into a bioactivity-based molecular networking (BBMN) to identify active compounds. The aerial stem extract of L. grandiflora showed the highest antibiofilm activity (>50% inhibition at 50 µg∙mL−1). The biological, chemical and BBMN investigations of its fractions highlighted nine ions correlated with the antibiofilm activity. The most correlated compound, identified as betulinic acid (BA), inhibited bispecies biofilms regardless of the three tested couples of strains (ATCC strains: >40% inhibition, clinical isolates: ≈27% inhibition), confirming its antibiofilm interest.

Mycotoxins are metabolites produced by molds that contaminate food commodities, are harmful to both humans and animals, as well as cause economic losses. Many countries have set regulatory limits and strict thresholds to control the level of mycotoxins in food and feedstuffs. New technologies and strategies have been developed to inhibit toxigenic fungal invasion and to decontaminate mycotoxins. However, many of these strategies do not sufficiently detoxify mycotoxins and leave residual toxic by-products. This review focuses on the use of phenolic compounds obtained from botanical extracts as promising bioagents to inhibit fungal growth and/or to limit mycotoxin yields. The mechanism of these botanicals, legislation concerning their use, and their safety are also discussed. In addition, recent strategies to overcome stability and solubility constraints of phenolic compounds to be used in food and feed stuffs are also mentioned., (© 2022 Institute of Food Technologists®.)

Genotoxic data of substances that could be used as food additives are required by the European Food Safety Authority. In this sense, the use of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99), due to its antioxidant and antibacterial activities, has been proposed as an alternative to sulfur dioxide in wine. The aim of this work was to study, for the first time, the in vivo genotoxic effects produced in rats orally exposed to 90, 180, or 360 mg ST-99/kg body weight at 0, 24, and 45 h. The combination of micronucleus assay in bone marrow (OECD 474) and standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach, liver, and blood of exposed animals. The ST-99 revealed no in vivo genotoxicity. These results were corroborated by analytical studies that confirm the presence of stilbenes and their metabolites in plasma and tissues. Moreover, to complete these findings, a histopathological study was performed under light microscopy in liver and stomach showing only slight modifications in both organs at the highest concentration used. The present work confirms that this extract is not genotoxic presenting a good profile for its potential application as a preservative in the wine industry.

Chemical investigation of the marine bryozoan Flustra foliacea collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W ( 1 - 7 ) and flustraminols C-H ( 8 - 13 ), and two new imidazole alkaloids, flustrimidazoles A and B ( 14 and 15 ), together with 12 previously described compounds ( 16 - 27 ). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure 2 was verified by calculations of the 13 C and 1 H NMR chemical shifts using density functional theory. The relative and absolute configurations of the new compounds were elucidated on the basis of coupling constant analysis, NOESY, [α] D , and ECD spectroscopic data, in addition to chemical derivatization. The compounds were tested for in vitro anti-inflammatory activity using a dendritic cell model. Eight compounds ( 1 , 3 , 5 , 13 , 16 , 18 , 26 , and 27 ) decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and two compounds ( 4 and 14 ) increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B ( 27 ) showed the most potent anti-inflammatory effect (IC 50 2.9 μM). These results demonstrate that F. foliacea from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity in vitro of metabolite 27 warrants further investigations into its potential as a lead for inflammation-related diseases.

Modulation of major histocompatibility complex (MHC) expression using drugs has been proposed to control immunity. Phytochemical investigations on Garcinia species have allowed the isolation of bioactive compounds such as polycyclic polyprenylated acylphloroglucinols (PPAPs). PPAPs such as guttiferone J ( 1 ), display anti-inflammatory and immunoregulatory activities while garcinol ( 4 ) is a histone acetyltransferases (HAT) p300 inhibitor. This study reports on the isolation, identification and biological characterization of two other PPAPs, i.e., xanthochymol ( 2 ) and guttiferone F ( 3 ) from Garcinia bancana , sharing structural analogy with guttiferone J ( 1 ) and garcinol ( 4 ). We show that PPAPs 1 - 4 efficiently downregulated the expression of several MHC molecules (HLA-class I, -class II, MICA/B and HLA-E) at the surface of human primary endothelial cells upon inflammation. Mechanistically, PPAPs 1 - 4 reduce MHC proteins by decreasing the expression and phosphorylation of the transcription factor STAT1 involved in MHC upregulation mediated by IFN-γ. Loss of STAT1 activity results from inhibition of HAT CBP/p300 activity reflected by a hypoacetylation state. The binding interactions to p300 were confirmed through molecular docking. Loss of STAT1 impairs the expression of CIITA and GATA2 but also TAP1 and Tapasin required for peptide loading and transport of MHC. Overall, we identified new PPAPs issued from Garcinia bancana with potential immunoregulatory properties.

Covering: up to 2019 Alkylresorcinols are amphiphilic metabolites, well-known for their diverse biological activities, produced by both prokaryotes and eukaryotes. A few classes of alkylresorcinol scaffolds have been reported from the photoautotrophic cyanobacteria, ranging from the relatively simple hierridins to the more intricate cylindrocyclophanes. Recently, it has emerged that cyanobacteria employ two different biosynthetic pathways to produce unique alkylresorcinol scaffolds. However, these convergent pathways intersect by sharing biosynthetic elements which lead to common structural motifs. To obtain a broader view of the biochemical diversity of these compounds in cyanobacteria, we comprehensively cover the isolation, structure, biological activity and biosynthesis of their mono- and dialkylresorcinols. Moreover, we provide an overview of the diversity and distribution of alkylresorcinol-generating biosynthetic gene clusters in this phylum and highlight opportunities for discovery of novel alkylresorcinol scaffolds. Because some of these molecules have inspired notable syntheses, different approaches used to build these molecules in the laboratory are showcased.

The metabolism of seaweeds depends on environmental parameters, the availability of nutrients, and biotic/abiotic stresses; therefore, their chemical composition fluctuates throughout the year. This study investigated seasonal variations in the metabolome of the Baltic Sea brown alga Fucus vesiculosus and its potential relation to the bioactivity profile. By using a definitive screening design (DSD) combined with pressurised liquid extraction (PLE), an optimised protocol was developed to extract algal biomass monthly for a full calendar year. An untargeted metabolomics approach using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS n )-based molecular networking and manual dereplication was employed. The extracts were simultaneously screened for their in vitro antimicrobial, anticancer/apoptotic, and free radical scavenging activities. 44 compounds were putatively dereplicated in the metabolome. Many compounds were found to vary with the sampling month; phlorotannin total ion count (TIC) was highest in summer, whilst chlorophylls, lipids, and carotenoids peaked in winter and spring. The greatest radical scavenging and apoptotic activities against pancreas cancer cells observed in the summer months were attributed to high phlorotannin TIC. Methicillin-resistant Staphylococcus aureus (MRSA) inhibitory activity was produced year-round without a clear seasonal trend. This is the first study applying DSD-based optimised PLE extraction combined with a metabolome analysis of F. vesiculosus for the identification of seasonal variations in both metabolome and bioactivity.

An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti . This includes three new metabolites, namely geobarrettin A⁻C ( 1 ⁻ 3 ) and four known compounds, barettin ( 4 ), 8,9-dihydrobarettin ( 5 ), 6-bromoconicamin ( 6 ), and l-6-bromohypaphorine ( 7 ) . The chemical structures of compounds 1 ⁻ 7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A ( 1 ) was assigned by ECD analysis and Marfey's method employing the new reagent l- N α -(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4⁺ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin ( 4 ) reduced DC secretion of IL-12p40 and IL-10 (IC 50 values 11.8 and 21.0 μM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.

In vivo confocal Raman microscopy (CRM), polarized light microscopy and Fourier transform infrared spectroscopy (FTIR) were used to determine if a significant amount of amorphous calcium carbonate (ACC) exists within larval shells of Baltic mytilid mussels ( Mytilus edulis -like) and whether the amount of ACC varies during larval development. No evidence for ACC was found from the onset of shell deposition at 21 h post-fertilization (hpf) until 48 hpf. Larval Mytilus shells were crystalline from 21 hpf onwards and exhibited CRM and FTIR peaks characteristic of aragonite. Prior to shell deposition at 21 hpf, no evidence for carbonates was observed through in vivo CRM. We further analysed the composition of larval shells in three other bivalve species, Mercenaria mercenaria , Crassostrea gigas and Crassostrea virginica and observed no evidence for ACC, which is in contrast to previous work on the same species. Our findings indicate that larval bivalve shells are composed of crystalline aragonite and we demonstrate that conflicting results are related to sub-optimal measurements and misinterpretation of CRM spectra. Our results demonstrate that the common perception that ACC generally occurs as a stable and abundant precursor during larval bivalve calcification needs to be critically reviewed., (© 2018 The Author(s).)

Geophagy, or the ingestion of earth or clay, is widespread among women of Sub-Saharan African, Caribbean or French Guiana origin. Little is known about this practice among HIV patients native of these countries and who are followed-up in France. The aims of this study were to determine (i) the prevalence and factors associated with geophagy among HIV patients native of these countries, (ii) patients' knowledge about the harmful effects of geophagy, and (iii) the association of geophagy with iron deficiency, or a history of anemia or constipation. Among the 119 included patients, current geophagy and previous geophagy were present in 11/119 (9%) and 47/119 (40%) patients, respectively. Female gender was the only factor associated with consumption (OR 5.37; 95% CI 2.07-15.92 p = 0.001). Awareness about the risk of iron-deficient anemia was low (24%). Preventive education should be integrated into the care of HIV adults from countries in which geophagy is a culture and widely accepted practice.

Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i.e., mammea coumarins, a biflavonoid, a pyranochromanone acid, a polyprenylated polycyclic acylphloroglucinol (PPAP) and two xanthones) were tested on resting and cytokine-activated EC cultures. Quantitative and qualitative changes in the expression of both adhesion molecules (VCAM-1, ICAM-1, E-selectin) and major histocompatibility complex (MHC) molecules have been used to measure their pharmaceutical potential. As a result, we identified 3 mammea coumarins that efficiently reduce (up to >90% at 10 μM) both basal and cytokine-regulated levels of MHC class I, class II, MICA and HLA-E on EC surface. They also prevented VCAM-1 induction upon inflammation. From a structural point of view, our results associate the loss of the free prenyl group substituting mammea coumarins with a reduced cellular cytotoxicity but also an abrogation of their anti-inflammatory potential and a reduction of their immunosuppressive effects. A PPAP, guttiferone J, also triggers a strong immunomodulation but restricted to HLA-E and MHC class II molecules. In conclusion, mammea coumarins with a free prenyl group and the PPAP guttiferone J emerge as NPs able to drastically decrease both VCAM-1 and a set of MHC molecules and to potentially reduce the immunogenicity of the endothelium., Competing Interests: The authors have declared that no competing interests exist.

Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led to a structural revision. Inspection of LC-DAD-MS(n) chromatograms allowed us to predict the presence of four new compounds, which were further isolated. Using spectroscopic methods (¹H-, (13)C- and 2D-NMR, HRMS, UV), these compounds were identified as new benzoyl substituted 4-phenylcoumarins (iso-pedilanthocoumarin B and neurophyllol C) and 4-(1-acetoxypropyl)coumarins cyclo F (ochrocarpins H and I).

Phytochemical investigation on the fruits of Mesua lepidota (Calophyllaceae) led to the isolation of seven new phenylcoumarin derivatives named lepidotols A-E (1-5) and lepidotins A and B (6, 7). These structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. Lepidotol A (1), the major compound, was evaluated for its inhibitory effect on inflammation and immunity using endothelial cell-based cellular assays. At 10 μM, 1 exhibited an anti-inflammatory activity, with a significant inhibition of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression induced by tumor necrosis factor-α. Lepidotol A also showed a mild immunosuppressive effect, with inhibition of the major histocompatibility complex molecules, namely, human leukocyte antigen (HLA)-DR and HLA-E.

We investigated measles humoral immunity levels in a cohort of HIV-infected adult patients in France and attempted to identify risk factors for antimeasles antibodies seronegativity. Being born after 1983 [odds ratio (OR) 4.40; 95% confidence interval (95% CI) 1.26-14.09; P = 0.0013] and a nadir CD4⁺ cell count below 100 cells/μl (OR 4.79; 95% CI 1.61-14.82; P = 0.0048) were the two factors independently associated with measles seronegativity. Systematic measles antibody screening should be performed in HIV-infected individuals born in the era of measles vaccination (after 1983 in France).

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Alkaloids from Thalictrum flavum L. (Ranuculaceae) growing in the Loire valley (France) were isolated and evaluated for their antiplasmodial and leishmanicidal activities. Berberine was identified as a major component but its analogue, pseudoberberine, was isolated for the first time from this plant. As far as bisbenzylisoquinolines are concerned, thalfoetidine was also isolated and, besides, its nor- derivative, northalfoetidine, was identified as a new compound. Previously isolated alkaloids from Thalictrum species such as northalidasine, northalrugosidine, thaligosidine, thalicberine, thaliglucinone, preocoteine, O-methylcassythine and armepavine were newly described in the roots of T. flavum. Tertiary isoquinolines, and particularly bisbenzylisoquinolines, were found to be leishmanicidal against L. major. Thalfoetidine appeared as the most potent but its new nor- derivative northalfoetidine, as well as northalidasine, were of particular interest due to the fact that their potential leishmanicidal activity was not associated to a strong cytotoxicity.

Using commercially available herpes simplex virus (HSV) type-specific serological diagnostic tests, HSV type 2 (HSV-2) antibody prevalence was assessed in two parallel prospective studies including 534 human immunodeficiency virus type 1 (HIV-1)-infected outpatients living in two areas of northern France. In the first cohort of 434 subjects, 223 (51%) individuals demonstrated a positive HSV-2 serological status while 66 (66%) of 100 subjects in the second cohort were seropositive for HSV-2 (51 versus 66%; P = 0.08). Among the 223 HSV-2-seropositive subjects identified in the first study cohort, only 22 (10%) had suffered from recurrent anogenital lesions during the past 12 months while 154 (69%) had no clinical history of herpesvirus infection. Our findings demonstrate high proportions of subclinical and undiagnosed HSV-2 infection in HIV-1-infected individuals and suggest that HSV type-specific serological testing in the French HIV-1-infected subpopulation could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections.

Objective: To report 6 cases of osteonecrosis in HIV-infected patients treated with highly active antiretroviral therapy (HAART) and compare the observed risk factors with those of published cases., Case Summaries: Osteonecrosis was diagnosed between 1999 and 2002 in 6 of 417 HIV-infected patients in our department of infectious diseases. At the time of diagnosis, mean patient age was 42 years, and 5 patients had developed AIDS. Mean CD4+ lymphocyte count was 563.5 cells/mm(3) and viral load was undetectable (<50 copies/mL) in 5 patients. The patients' mean body mass index was 22.5 kg/m(2). Four had lipodystrophy. All were receiving HAART, including a protease inhibitor in 4 patients; the remaining 2 patients had a history of protease inhibitor treatment. Median time from the first antiretroviral therapy to osteonecrosis diagnosis was 46.5 months. Established risk factors were the use of corticosteroids in 2 patients and dyslipidemia in all patients. All of the patients developed pain and functional impotence of the hip or ankle joints. Osteonecrosis of the hip was bilateral in 4 cases. Three patients required surgical intervention, all of whom had favorable outcomes., Discussion: HIV-infected patients are at a higher risk for the development of osteonecrosis and are more likely to be exposed to predisposing factors to its development. The HAART implication as a predisposing factor remains controversial., Conclusions: The pathogenesis of osteonecrosis in HIV-infected individuals may be multifactorial; the reasonable approach for clinicians consists of treating concomitant predisposing conditions that might further cause osteonecrosis.

Aim of the Study: The American College of Rheumatology (ACR) has proposed a list of criteria for diagnosis of giant cell arteritis in order to guide clinical research by differentiating it from other vasculitis. The aim of this retrospective investigation, based on the findings of 415 temporal artery biopsies was to assess the diagnostic value of these criteria in the daily clinical setting., Methods: The demographic, clinical and biological characteristics of patients with positive (confirmed cases of giant cell arteritis) or negative (controls) histopathological temporal artery biopsy findings were analyzed using downward step-by-step logistic regression analysis. This analysis enabled investigators to list signs with inherent diagnostic value. Based their odds-ratio, these factors were used to determine a clinical score for giant cell arteritis., Results: A score of over 7 - out of a maximum score of 32 - enables the diagnosis for giant cell arteritis with the best possible compromise between a sensitivity of 75.7% and a specificity of 72.2%. ACR criteria had a sensitivity of 97.5% and a specificity of 78.9% when used in our patient group., Conclusion: Our study results are original in that the control group was composed of patients in whom the diagnosis of giant cell arteritis had been suggested but refuted by the absence of histopathological findings on the temporal artery biopsy. This pragmatic attitude in selecting the control group may explain the difference observed with the ACR criteria in terms of sensitivity and specificity. Further research is needed to develop a diagnostic method for giant cell arteritis without resorting to temporal artery biopsy.

One hundred eighteen Candida clinical isolates from human immunodeficiency virus-infected patients were tested for their susceptibilities to fluconazole and itraconazole by Fungitest and the National Committee for Clinical Laboratory Standards MIC method. Fungitest results depended on both yeast species and antifungal agents. This test is able to detect sensitive strains (97% agreement with results of the MIC method in tests with fluconazole and 84% agreement in tests with itraconazole) but has a poor capacity to detect resistant strains (26% agreement in tests with fluconazole and 5% agreement in tests with itraconazole).