Superficial fungal infections in the south of France-is fusariosis the next emergent onychopathy?

In France, onychomycoses represent about 30% of superficial mycoses seen by dermatologists. In recent years, an increased number of mycoses have been observed due to non-dermatophytic moulds. The purpose of this study was to evaluate the epidemiological profile of identified superficial fungal infections in the Laboratory of Parasitology-Mycology of the University Hospital of Nice over a 2-year period. A retrospective study was performed from the nail, skin, and scalp samples of patients analyzed from January 2018 to December 2019. In this study, 3074 samples (54.2% nails, 39.7% skin, and 6.1% scalp) were analyzed representing 1922 patients. Among them, 809 (42.1%) patients were sampled by dermatologists and 1113 (57.9%) were sampled by our experts in the clinical unit of the University Hospital of Nice. In total, 1159 (37.7%) samples had a positive culture (1195 strains identified) including 712 (59.6%) dermatophytes, 345 (28.9%) yeasts, and 138 (11.5%) other filamentous moulds. Trichophyton rubrum was the main dermatophyte (563; 47.1%) followed by T. interdigitale (84; 7.0%), and T. soudanense (25; 2.1%). Yeasts were mostly represented by Candida albicans (155; 13.0%). Among the other moulds, Fusarium sp. was the most isolated (61; 5.1%). Dermatophytes stay predominant in superficial fungal infections where the anthropophilic species T. rubrum was found in almost half of the positive cultures. Interestingly, moulds represented an important part of infections in our population. This study highlights the increasing share of Fusarium sp. superficial fungal infection in our patients' population, perhaps requiring a major therapeutic adaptation in the years to come.

We assessed the epidemiological profile of superficial fungal infections in the Laboratory of Parasitology­Mycology of the Hospital of Nice, over a 2-year period. Among our samples, dermatophytes remain predominant, mainly the species Trichophyton rubrum and we had a large proportion of Fusarium.

Commiphora wildii Merxm. Essential Oil: Natural Heptane Source and Co-Product Valorization.

As an alternative to fossil volatile hydrocarbon solvents used nowadays in perfumery, investigation on essential oil of Commiphora wildii Merxm. oleo gum resin as a source of heptane is reported here. Heptane, representing up to 30 wt-% of this oleo gum resin, was successfully isolated from the C. wildii essential oil, using an innovative double distillation process. Isolated heptane was then used as a solvent in order to extract some noble plants of perfumery. It was found that extracts obtained with this solvent were more promising in terms of sensory analysis than those obtained from fossil-based heptane. In addition, in order to valorize the essential oil depleted from heptane, chemical composition of this oil was found to obtain, and potential biological activity properties were studied. A total of 172 different compounds were identified by GC-MS in the remaining oil. In vitro tests-including hyaluronidase, tyrosinase, antioxidant, elastase and lipoxygenase, as well as inhibitory tests against two yeasts and 21 bacterial strains commonly found on the skin-were carried out. Overall, bioassays results suggest this heptane-depleted essential oil is a promising active ingredient for cosmetic applications.

A new software tool for planning interventional procedures in liver cancer.

INTRODUCTION: Intra-arterial therapy is an effective way of performing chemotherapy or radiation therapy in patients with primary liver cancer (i.e. hepatocellular carcinoma). Although this minimally invasive approach is now an established treatment option, support tools for pre-operative planning and intra-operative assistance might be helpful. MATERIAL AND METHODS: We developed an approach for semi-automatic segmentation of computed tomography angiography images of the main arterial branches (required for access path to the treatment site), automatic segmentation of the liver, arterial and venous tree, and interactive segmentation of the tumors (required for procedure-specific planning). This approach was then integrated into a liver-specific workflow within EndoSize® solution, a planning software for endovascular procedures. The main branches extraction approach was qualitatively evaluated inside the software, while the automatic segmentation methods were quantitatively assessed. RESULTS: Main branches extraction provides a success rate of 85% (i.e. all arteries correctly extracted) in a dataset of 172 patients. On public databases, a mean DICE of 0.91, 0.47 and 0.92 was obtained for liver, venous and arterial trees segmentation, respectively. CONCLUSIONS: This pipeline is suitable for directly accessing the treatment site, giving anatomic measurements, and visualizing the hepatic trees, liver, and surrounding arteries during the pre-operative planning. ABBREVIATIONS: HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; CT: computed tomography; CTA: computed tomography angiography; AMS: superior mesenteric artery; LGA: left gastric artery; RHA: right hepatic artery; LHA: left hepatic artery; rbHA: right branch of the hepatic artery; lbHA: left branch of the hepatic artery; GDA: gastroduodenal artery; VOI: volume of interest; SD: standard deviation; MICCAI: medical image computing and computer assisted interventions; MR: magnetic resonance.

UHPLC-HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities.

Lichens are complex symbiotic organisms able to produce a vast array of compounds. The Algerian lichen diversity has only prompted little interest even given the 1085 species listed. Herein, the chemodiversity of four Algerian lichens including Cladonia rangiformis, Ramalina farinaceae, R. fastigiata, and Roccella phycopsis was investigated. A dereplication strategy, using ultra high performance liquid chromatography-high resolution-electrospray ionization-mass spectrometry (UHPLC-HRMS/MS), was carried out for a comprehensive characterization of their substances including phenolics, depsides, depsidones, depsones, dibenzofurans, and aliphatic acids. Some known compounds were identified for the first time in some species. Additionally, the lichenic extracts were evaluated for their antifungal and antimicrobial activities on human pathogenic strains (Candida albicans, C. glabrata, Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli). Cyclohexane extracts were found particularly active against human pathogenic fungi with MIC80 values ranging from 8 to 62.5 µg/mL, without cytotoxicity. This study highlights the therapeutic and prophylactic potential of lichenic extracts as antibacterial and antifungal agents.

Nano-Ayurvedic Medicine Approaches Using Ginkgo biloba-Phytochemicals Functionalized Gold Nanoparticles Against Breast Cancer.

Purpose: Breast cancer is a significant global health issue, contributing to 15% of cancer-related deaths. Our laboratory has pioneered a novel approach, combining Ayurvedic principles with green nanotechnology, to develop a scientifically rigorous medical modality referred to as Nano-Ayurvedic Medicine, recently approved by the US Patents and Trademarks Office. Here in we report a new Nano-Ayurvedic medicine agent derived from gold nanoparticles encapsulated with phytochemicals from Ginkgo biloba plant (GB-AuNPs). Methods: We have developed biocompatible gold nanoparticles using electron-rich phytochemicals from Ginkgo biloba as reducing agent cocktail. Ginkgo biloba phytochemical-encapsulated gold nanoparticles (GB-AuNPs) were fully characterized, and their anticancer activity, including immunomodulatory profiles, were evaluated against breast (MDAMB-231) cancer cell lines. Results: Characterization revealed spherical morphology for GB-AuNPs and possessed optimum in vitro stability through high zeta potential of -34 mV for optimum in vivo stability. The core size of GB-AuNPs of 19 nm allows for penetration into tumor cells through both EPR effects as well as through the receptor-mediated endocytosis. The Antitumor efficacy of this nano-ayurvedic medicine agent revealed strong antitumor effects of GB-AuNPs towards MDAMB-231. Our investigations reveal that GB-AuNPs enhance anti-tumor cytokines (IL-12, TNF-α, IFN-γ) and reduce pro-tumor cytokines (IL-10, IL-6), promoting the conversion of protumor M2 macrophages into M1-like macrophage antitumor phenotype. Cellular studies show that GB-AuNPs offer superior anti-tumor efficacy and a better safety profile against breast tumors compared to cisplatin. Conclusion: Our investigations have demonstrated that the nano-ayurvedic medicine agent, GB-AuNPs, treats cancers through an immunomodulatory mechanism facilitated by elevated levels of anti-tumor cytokines (TNF-α, IFN-γ and IL-12) with concomitant downregulation of pro-tumor cytokines expression (IL-6 and IL-10). The green nanotechnology approach for the development of nano-ayurvedic medicine agent (GB-AuNPs), as described in this paper, presents new and attractive opportunities for treating human cancers and other debilitating diseases and disorders.

Cyclopeptide mushroom poisoning: A retrospective series of 204 patients.

Cyclopeptide mushroom poisoning is responsible for 90%-95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression. We included 204 cases of amatoxin toxicity. More than three-quarters developed an increase in AST and/or ALT (78.1%), and over half developed a decrease in prothrombin ratio (<70%: 53%) and/or Factor V (<70%: 54%). One-third developed an acute renal injury (AKI). Twelve patients (5.9%) developed post-poisoning sequelae (persistent kidney injury more than 1 month after ingestion and liver transplant). Five patients (2.5%) received a liver transplant, and nine died (4.4%). The mean time to onset of digestive disorders was shorter in PSS2 and PSS3-4 patients (10.9 ± 3.9/11.3 ± 6.3 h) than in PSS1 patients (14 ± 6.5 h; p < 0.05). Patients who died or developed post-poisoning sequelae had more frequent cardiovascular comorbidities compared with recovered patients (60.0% versus 29.5%; p < 0.01).

Preparative isolation, fast centrifugal partition chromatography purification and biological activity of cajaflavanone from Derris ferruginea stems.

INTRODUCTION: The Derris genus is known to contain flavonoid derivatives, including prenylated flavanones and isoflavonoids such as rotenoids, which are generally associated with significant biological activity. OBJECTIVE: To develop an efficient preparative isolation procedure for bioactive cajaflavanone. METHODOLOGY: Fast centrifugal partition chromatography (FCPC) was optimised to purify cajaflavanone from Derris ferruginea stems in a single step as compared to fractionation from the cyclohexane extract by successive conventional solid-liquid chromatography procedures. The purification yield, purity, time and solvent consumption per procedure are described. The anti-fungal, anti-bacterial, anti-leishmanial, anti-plasmodial, anti-oxidant activities and the inhibition of advanced glycation end-products (AGEs) by cajaflavanone accumulation are described. RESULTS: FCPC enabled cajaflavanone purification in a single separation step, yielding sufficient quantities to perform in vitro biological screening. Interestingly, cajaflavanone had an inhibitory effect on the formation of AGEs, without displaying any in vitro anti-oxidant activity. CONCLUSION: A simple and efficient procedure, in comparison with other preparative methods, for bioactive cajaflavone purification has been developed using FCPC.

New method for screening anti-Leishmania compounds in plants extracts by HPTLC-bioautography.

Leishmania genus is responsible for leishmaniasis, a group of diseases affecting 12 million people in the tropical and subtropical zone. Currently, the few drugs that are available to treat this disease are expensive and cause many side effects. Searching for new therapeutics from plant species seems to be a promising path. This work proposes an original HPTLC test against parasites, in particular on Leishmania infantum, to screen new molecules from plant extracts. The technique uses protozoa transformed to express the luciferase gene to observe the bioautogram in bioluminescence. We have developed two different test protocols based on the two dimorphic stages of the parasite. The free promastigote stage, and an intracellular stage parasitizing macrophage cells called the amastigote stage. These two stages only survive under extremely different conditions which required the development of two very different test protocols. For the promastigote free stage of the protozoa, the direct bioautography technique was chosen while for the intracellular amastigote stage, bioautography by immersion (agar overlay) was required. Amphotericine B was chosen as the reference compound for this assay. The development of each of these two tests made it possible to clearly detect areas of activity on the bioautogram, allowing a rapid and inexpensive screening of the antiparasitic properties of molecules in natural extracts.

Solidago virgaurea L. Plant Extract Targeted Against Candida albicans to Reduce Oral Microbial Biomass: a Double Blind Randomized Trial on Healthy Adults.

Oral microbiome plays an important part on oral health and endogenous bacteria and fungi should not be eradicated. However, their proliferation must be controlled by oral hygiene care. In vitro, Solidago virgaurea ssp. virgaurea L. (SV) plant extract inhibits the adherence and hyphal formation of a fungus, Candida albicans. It reduces the biomass of Candida-bacterial biofilms but not fungal or bacterial growth. Unlike chemical antiseptics, like triclosan and chlorhexidine for instance, SV is a plant extract easily biodegradable. The purpose of this study was to assess the in vivo effectiveness of SV extract in reducing oral biomass. A randomized, double-blind clinical study, with dental plaque evaluation designed to assess the effectiveness of a fluorinated toothpaste containing SV (Bucovia™, Givaudan, Vernier, Switzerland) was conducted. Sixty-six subjects (SV group n = 33 vs. control n = 33) brushed their teeth twice a day for a 4-week period. Supragingival dental plaque was sampled. Total bacterial load (broad spectral bacterial quantitative Polymerase Chain Reaction (qPCR)), C. albicans and seven bacterial species were quantified by qPCR. In the Intervention group, there was a decrease of Total bacterial load (ΔD0D28 p = 0.005 and ΔD14D28 p = 0.026), Streptococcus mutans (ΔD0D14 p = 0.024) and C. albicans (ΔD0D28 p = 0.022). In the Control group Total bacterial load tended to decrease from baseline to day 28 (ΔD0D28 p = 0.062 and ΔD14D28 p = 0.009). Plaque Index and Gingival Index improved in both groups.

Hydroxamate siderophores of Scedosporium apiospermum.

Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis and causing severe infections in immunocompromised hosts. In order to improve our knowledge on the pathogenic mechanisms of this fungus, we investigated the production of siderophores. Cultivation on CAS medium and specific assays for different classes of siderophores suggested the secretion of hydroxamates. A maximal production was obtained by cultivation of the fungus at alkaline pH in an iron-restricted liquid culture medium. Siderophores were then extracted from the culture filtrate by liquid/liquid extraction, and separated by reverse phase high performance liquid chromatography. Two siderophores, dimerumic acid and Nα-methyl coprogen B, were identified by electrospray ionization-mass spectrometry and MS-MS fragmentation. Finally, comparison of various strains suggested a higher production of Na-methyl coprogen B by clinical isolates of respiratory origin. Studies are initiated in order to determine the potential usefulness of these siderophores as diagnostic markers of scedosporiosis.

Synthesis, characterization and antifungal activity of a series of manganese(II) and copper(II) complexes with ligands derived from reduced N,N'-O-phenylenebis(salicylideneimine).

A series of manganese(II) and copper(II) complexes with reduced Schiff bases derived from o-phenylenediamine has been prepared and characterized by elemental analysis, TG measurements, ESR, magnetic measurements, FTIR, UV-Visible spectra and conductivity. These complexes were found to be [MnL(H2O)n] and [CuL](H2O)n species with n=0-2. Their antifungal activity was evaluated on different human fungi including yeasts of the Candida genus (C. albicans, C. glabrata, C. tropicalis and C. parapsilopsis) some opportunistic moulds belonging to the Aspergillus (A. fumigatus, A. terreus and A. flavus), Scedosporium genus (S. apiospermum and S. prolificans) and some dermatophytes (M. gypseum, M. persicolor, T. mentagrophytes, M. canis and T. tonsurans). The manganese complexes showed a significant growth inhibition of the dermatophytes tested and fungi of the genus Scedosporium. This is very interesting as these fungi are usually poorly susceptible to current antifungal including Amphotericin B and Itraconazole chosen as reference in this study.

Synthesis of new 1-[2-Azido-2-(2,4-dichlorophenyl)ethyl]-1H/-imidazoles and in vitro evaluation of their antifungal activity.

New 1-[2-azido-2-(2,4-dichlorophenyl)ethyl]-1H/-imidazole were synthesized by nucleophilic substitution of various tertiary alcohols with azide anion in presence of boron trifluoride-diethyl etherate. Their antifungal activity was evaluated against Candida albicans, Candida glabrata, Aspergillus fumigatus and an azole-resistant petite mutant of C. glabrata. Preliminary SAR results are discussed.

Peptaibols: stable markers of fungal development in the marine environment.

Different peptaibols were observed in both fresh and frozen marine sediments collected from a marine area devoted to bivalve culture (Fier d'Ars, Atlantic coast, France). The identification of the peptaibols was based on a three-step mass-spectrometric analysis: observation of doubly charged ions with a characteristic isotopic profile, cleavage and observation of C- and N-terminal fragments, and partial sequencing of the N-terminal segments. The MS characteristics indicated numerous similarities between the peptaibols detected and those produced by different strains of Trichoderma species isolated from fresh sediments. Peptaibols were also detected in mussel samples collected at the same site. This constitutes the first observation of contamination of the marine human-food chain by fungal metabolites. Since peptaibols were readily observed both in fresh sediments and in samples kept frozen for several years, these compounds can be considered as stable markers of the development of Trichoderma in the marine environment.

Vetiver Essential Oil in Cosmetics: What Is New?

Background: Vetiver is a key ingredient for the perfume industry nowadays. However, with the constant and rapid changes of personal tastes, this appeal could vanish and this sector could decline quite quickly. New dissemination paths need to be found to tap this valuable resource. Methods: In this way, its potential use in cosmetics either as an active ingredient per se (with cosmeceutical significance or presenting antimicrobial activity) has hence been explored in vitro. Results: In this contribution, we demonstrated that vetiver essential oil displays no particularly significant and innovative cosmetic potential value in formulations apart from its scent already largely exploited. However, evaluated against twenty bacterial strains and two Candida species using the in vitro microbroth dilution method, vetiver oil demonstrated notably some outstanding activities against Gram-positive strains and against one Candida glabrata strain. Conclusions: Based on these findings, vetiver essential oil appears to be an appropriate aspirant for the development of an antimicrobial agent for medicinal purposes and for the development of a cosmetic ingredient used for its scent and displaying antimicrobial activity as an added value.

The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii.

Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity that may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high-performance liquid chromatography and high-resolution electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together, these results suggest that this six-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis.

Three 1-thio-beta-D-glucopyranosides from the seeds of Afrostyrax lepidophyllus Mildbr.

Three new 1-thioglycosides namely methylthiomethyl 1-thio-beta-D-glucopyranoside (Afrostyraxthioside A), methylsulfonylmethyl 1-thio-beta-D-glucopyranoside (Afrostyraxthioside B) and methylsulfonylmethylthiomethyl 1-thio-beta-D-glucopyranoside (Afrostyraxthioside C) were isolated from the seeds of Afrostyrax lepidophyllus Mildbr. Their structures were mainly elucidated by using one- and two-dimensional NMR and mass spectroscopies and also by an efficient one-step synthesis. Moreover, Afrostyraxthiosides A, B and C constitute a new subclass of 1-thioglycosides isolated from natural sources.

Normal phase HPLC-based activity profiling of non-polar crude plant extracts - acetylcholinesterase inhibiting guttiferones from Montrouziera cauliflora as a case study.

The study describes bioactive compounds as inhibitors of acetylcholinesterase (AChE), from the stem bark extract of Montrouziera cauliflora, selected among 19 dichloromethane extracts from Clusiaceae species. Our work focused on the development of an original normal phase HPLC microfractionation strategy to rapidly assess highly active zones from this crude active non-polar plant extract. Two different microfraction collection methods were evaluated for the assessment of the AChE inhibition. Two guttiferones and a tocotrienol were directly isolated among five compounds identified off-line by NMR after upscaling the fractionation and their AChE inhibition was evaluated. The strengths and weaknesses of the two microfractionation collection methods for HPLC-AChE activity-based profiling are discussed.

Antileishmanial and antifungal activities of xanthanolides isolated from Xanthium macrocarpum.

Seven xanthanolides, xanthinosin, xanthatin, 4-hydroxyxanthinosin, xanthinin, 4-epiisoxanthanol, 4-epixanthanol, 2-hydroxyxanthinosin and 4-oxobedfordia acid, were isolated from the fruits of Xanthium macrocarpum. A valuation of the antifungal activity of these xanthanolides against Candida albicans, Candida glabrata and Aspergillus fumigatus and of their antileishmanial activity against Leishmania infantum and Leishmania mexicana is presented.

Antifungal and antibacterial metabolites from a French poplar type propolis.

During this study, the in vitro antifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains including Staphylococcus aureus. Organic extracts showed a significant antifungal activity against C. albicans and C. glabrata (MIC80 between 16 and 31 µg/mL) but only a weak activity towards A. fumigatus (MIC80 = 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially against S. aureus (SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100 30-97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study.

Combined use of LC/MS and a biological test for rapid identification of marine mycotoxins produced by Trichoderma koningii.

Trichoderma koningii Oudemans, a strain isolated from a shellfish farming area, was selected for its high frequency in samples and its ability to produce metabolites when cultured in natural seawater. Combined use of LC/MS and a biological test on blowfly larvae allowed the characterization of four compounds after purification in only two steps (VLC and HPLC). ESI/MS, a powerful tool for rapid identification and sequence determination of peptides, confirmed that these compounds were peptide, alpha-aminoisobutyric acid and amino alcohol (peptaibols), the usual metabolites of Trichoderma.