Antibacterial and anti-coronavirus investigation of selected Senegalese plant species according to an ethnobotanical survey.

ETHNOPHARMACOLOGICAL RELEVANCE: In Senegal, upper and lower respiratory tract infections constitute a real health problem. To manage these disorders, most people rely on the use of local medicinal plants. This is particularly the case for species belonging to the botanical families, Combretaceae, Fabaceae, Myrtaceae and Rubiaceae, which are widely used to treat various respiratory problems such as colds, flu, rhinitis, sinusitis, otitis, angina, bronchitis, bronchiolitis and also pneumonia. AIM OF THE STUDY: The aim of this study was to identify medicinal plants traditionally used for the management of infectious diseases, in particular those of the respiratory tract. On the basis of these ethnopharmacological uses, this study made it possible to highlight the antibacterial, antiviral and cytotoxic activities of selected plant species. MATERIALS AND METHODS: An ethnobotanical survey was conducted in Senegal among informants, including herbalists, traditional healers, and households, using medicinal plants in the management of infectious diseases, with a focus on respiratory tract infections. The most cited plant species were evaluated in vitro on a panel of 18 human pathogenic bacteria may be involved in respiratory infections and against the human coronavirus HCoV-229E in Huh-7 cells. The antiviral activity of the most active extracts against HCoV-229E was also evaluated on COVID-19 causing agent, SARS-CoV-2 in Vero-81 cells. In parallel, cytotoxic activities were evaluated on Huh-7 cells. RESULTS: A total of 127 informants, including 100 men (78.74%) and 27 women (21.26%) participated in this study. The ethnobotanical survey led to the inventory of 41 plant species belonging to 19 botanical families used by herbalists and/or traditional healers and some households to treat infectious diseases, with a specific focus on upper respiratory tract disorders. Among the 41 plant species, the most frequently mentioned in the survey were Guiera senegalensis J.F. Gmel. (95.2%), Combretum glutinosum Perr. Ex DC. (93.9%) and Eucalyptus spp. (82.8%). Combretaceae (30.2%) represented the most cited botanical family with six species, followed by Fabaceae (29.3%, 12 species). A total of 33 crude methanolic extracts of the 24 plant species selected for their number of citations were evaluated in vitro for their antimicrobial and cytotoxic activities. Guiera senegalensis, Combretum glutinosum, Vachellia nilotica subsp. tomentosa (Benth.) Kyal. & Boatwr, Eucalyptus camaldulensis Dehnh., and Terminalia avicennioides Guill. & Perr., showed antibacterial activities. The most active plants against HCoV-229E were: Ficus sycomorus L., Mitragyna inermis (Willd.) Kuntze, Pterocarpus erinaceus Poir., and Spermacoce verticillata L. One of these plants, Mitragyna inermis, was also active against SARS-CoV-2. CONCLUSION: This work confirmed the anti-infective properties of plant species traditionally used in Senegal. Overall, the most frequently cited plant species showed the best antibacterial activities. Moreover, some of the selected plant species could be considered as a potential source for the management of coronavirus infections. This new scientific data justified the use of these plants in the management of some infectious pathologies, especially those of the respiratory tract.

Therapeutic Potential of Chlorhexidine-Loaded Calcium Hydroxide-Based Intracanal Medications in Endo-Periodontal Lesions: An Ex Vivo and In Vitro Study.

Endo-periodontal lesions are challenging clinical situations where both the supporting tissues and the root canal of the same tooth are infected. In the present study, chlorhexidine (CHX)-loaded calcium hydroxide (CH) pastes were used as intracanal medications (ICMs). They were prepared and tested on pathogens found in both the root canal and the periodontal pocket. Exposure to 0.5% and 1% CHX-loaded ICMs decreased the growth of Porphyromonas gingivalis and was effective in eradicating or inhibiting an Enterococcus faecalis biofilm. CH was injected into the root canal of extracted human teeth immersed in deionized water. CHX-loaded ICMs resulted in the transradicular diffusion of active components outside the tooth through the apex and the lateral dentinal tubules, as shown by the release of CHX (from 3.99 µg/mL to 51.28 µg/mL) and changes in pH (from 6.63 to 8.18) and calcium concentrations (from 2.42 ppm to 14.67 ppm) after 7 days. The 0.5% CHX-loaded ICM was non-toxic and reduced the release of IL-6 by periodontal cells stimulated by P. gingivalis lipopolysaccharides. Results indicate that the root canal may serve as a reservoir for periodontal drug delivery and that CHX-based ICMs can be an adjuvant for the control of infections and inflammation in endo-periodontal lesions.

Injectable Chitosan-Based Hydrogels for Trans-Cinnamaldehyde Delivery in the Treatment of Diabetic Foot Ulcer Infections.

Diabetic foot ulcers (DFU) are among the most common complications in diabetic patients and affect 6.8% of people worldwide. Challenges in the management of this disease are decreased blood diffusion, sclerotic tissues, infection, and antibiotic resistance. Hydrogels are now being used as a new treatment option since they can be used for drug delivery and to improve wound healing. This project aims to combine the properties of hydrogels based on chitosan (CHT) and the polymer of ß cyclodextrin (PCD) for local delivery of cinnamaldehyde (CN) in diabetic foot ulcers. This work consisted of the development and characterisation of the hydrogel, the evaluation of the CN release kinetics and cell viability (on a MC3T3 pre-osteoblast cell line), and the evaluation of the antimicrobial and antibiofilm activity (S. aureus and P. aeruginosa). The results demonstrated the successful development of a cytocompatible (ISO 10993-5) injectable hydrogel with antibacterial (99.99% bacterial reduction) and antibiofilm activity. Furthermore, a partial active molecule release and an increase in hydrogel elasticity were observed in the presence of CN. This leads us to hypothesise that a reaction between CHT and CN (a Schiff base) can occur and that CN could act as a physical crosslinker, thus improving the viscoelastic properties of the hydrogel and limiting CN release.

Antiviral functionalization of a polypropylene nonwoven textile structure as a self-decontaminating layer for respiratory masks.

The aim of this work was to develop a filtering biocidal polypropylene (PP) nonwoven textile structure to block and inactivate airborne bacteria and viruses. PP filters were functionalized with a cyclodextrin (CD)-polycarboxylic acid-crosslinked polymer (PP-CD) through a pad/dry/curing process, and were then activated by padding in an alkyl dimethyl benzalkonium chloride (ADBAC) solution. The textile finishing process parameters were optimized with the perspective of mass production, considering the threshold temperature necessary for provoking crosslinking and the limitation of the low thermal stability of PP. The use of an aqueous solution containing hydroxypropyl-ß-cyclodextrin (HPßCD), 1,2,3,4-butanetetracarboxylic acid (BTCA), ammonium hypophosphite (AH), and a surfactant allowed immobilization of the optimal quantity of cyclodextrin polymer under curing for 5 minutes at 125 °C without affecting the nonwoven PP structure. The presence of CD drastically increased the sorption of ADBAC on the textiles. There was leaching of ADBAC at the first rinsing and then satisfactory fastness at the second and third rinsings, revealing adsorption mechanisms by weak physical interactions, ionic interactions, and inclusion of ADBAC inside the CD cavities. SEM revealed no clogging of the nonwoven pores, nor any increase in the air flow resistance, as evaluated by pressure drop measurements. The filtration efficiency of particulate matter PM3.0 and PM0.5 was moderately affected, in contrast to that of PM0.3, which greatly decreased due to the loss of the electrostatic charge of the filter upon the functionalization process. Bactericidal tests resulted in a reduction of 3 log10 against Staphylococcus aureus, and for virucidal tests on human coronavirus HCoV-229E, there was a reduction of 3.4 log10, with both strains undergoing 20 minutes of contact. Finally, the filter we developed is manufacturable by a scalable process, and because of its filtration and biocidal performances, it is a choice material as a self-disinfecting layer in the fabrication of facepiece respirators.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats.

BACKGROUND: Postoperative recurrence (POR) after ileocecal resection (ICR) affects most Crohn's disease patients within 3-5 years after surgery. Adherent-invasive Escherichia coli (AIEC) typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis. Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut. AIM: To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic (TgB27) rat model. METHODS: Sixty-four rats [strain F344, 38 TgB27, 26 control non-Tg (nTg)] underwent an ICR at the 12th wk (W12) of life and were sacrificed at the 18th wk (W18) of life. TgB27 rats were challenged daily with oral administration of LF82 (109 colony forming units (CFUs)/day (d), n = 8), PBS (n = 5), CNCM I-3856 (109 CFUs/d, n = 7) or a combination of LF82 and CNCM I-3856 (n = 18). nTg rats receiving LF82 (n = 5), PBS (n = 5), CNCM I-3856 (n = 7) or CNCM I-3856 and LF82 (n = 9) under the same conditions were used as controls. POR was analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal LF82 quantifications were performed weekly for each animal. Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18. Data are expressed as the median with the interquartile range. RESULTS: nTg animals did not develop POR. A total of 7/8 (87%) of the TgB27 rats receiving LF82 alone had POR (macroscopic score ≥ 2), which was significantly prevented by CNCM I-3856 administration [6/18 (33%) TgB27 rats, P = 0.01]. Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5 (2 - 4). Seven out of 18 TgB27 rats (39%) receiving CNCM I-3856 and LF82 had no macroscopic lesions. Compared to untreated TgB27 animals receiving LF82 alone, coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic [3.5 (2 - 4) vs 1 (0 - 3), P = 0.002] and histological lesions by more than 50% [4.5 (3.3 - 5.8) vs 2 (1.3 - 3), P = 0.003]. The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats (r = 0.49, P = 0.006), with a higher risk of POR in animals having high levels of luminal LF82 (71.4% vs 25%, P = 0.02). Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82, increased the production of interleukin (IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats. CONCLUSION: In a reliable model of POR induced by LF82 in TgB27 rats, CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model.

BACKGROUND AND AIMS: Adherent invasive Escherichia coli [AIEC] are recovered with a high frequency from the gut mucosa of Crohn's disease patients and are believed to contribute to the dysbiosis and pathogenesis of this inflammatory bowel disease. In this context, bacteriophage therapy has been proposed for specifically targeting AIEC in the human gut with no deleterious impact on the commensal microbiota. METHODS: The in vitro efficacy and specificity of a seven lytic phage cocktail [EcoActive™] was assessed against [i] 210 clinical AIEC strains, and [ii] 43 non-E. coli strains belonging to the top 12 most common bacterial genera typically associated with a healthy human microbiome. These data were supported by in vivo safety and efficacy assays conducted on healthy and AIEC-colonized mice, respectively. RESULTS: The EcoActive cocktail was effective in vitro against 95% of the AIEC strains and did not lyse any of the 43 non-E. coli commensal strains, in contrast to conventional antibiotics. Long-term administration of the EcoActive cocktail to healthy mice was safe and did not induce dysbiosis according to metagenomic data. Using a murine model of induced colitis of animals infected with the AIEC strain LF82, we found that a single administration of the cocktail failed to alleviate inflammatory symptoms, while mice receiving the cocktail twice a day for 15 days were protected from clinical and microscopical manifestations of inflammation. CONCLUSIONS: Collectively, the data support the approach of AIEC-targeted phage therapy as safe and effective treatment for reducing AIEC levels in the gut of IBD patients.

Antimicrobial Properties of Compounds Isolated from Syzygium malaccense (L.) Merr. and L.M. Perry and Medicinal Plants Used in French Polynesia.

A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat "infectious" diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical species Syzygium malaccense (Myrtaceae) for phytochemical analysis. Leaves of Syzygium malaccense were usually used in mixture with rhizomes of Curcuma longa to treat infectious diseases such as cystitis. The methanolic plant extracts were tested in vitro with an agar microdilution method on 33 bacteria strains and 1 yeast to obtain their Minimal Inhibitory Concentration (MIC), and cytotoxicity against HepG2 cells were evaluated. Antimicrobial synergistic effects of methanolic plant extracts from leaves of Syzygium malaccense and rhizomes from Curcuma longa were also evaluated. The bio-guided isolation of leaf extract from Syzygium malaccense led to the identification of seven alkyl-salicylic acids (anacardic acids or ginkgolic acids C15:0, C15:1, C17:0, C17:1, C17:2, C17:3 and C19:1) described for the first time in this species. All compounds were tested against Staphylococcus aureus (18.75 < MIC < 75.0 µg/mL), Streptococcus pyogenes (2.34 < MIC < 18.75 µg/mL) and Pseudomonas aeruginosa (MIC = 150 µg/mL), and their structure−activity relationships were discussed. The methanolic extract and salicylic derivatives from S. malaccense showed an interesting antimicrobial activity against Gram+ bacteria, without toxicity on hepG2 cells at 400 µg/mL. Moreover, these antibacterial compounds have already been studied for their anti-inflammatory activity, which supports the therapeutic interest of S. malaccense against infectious diseases.

Core-Sheath Electrospun Nanofibers Based on Chitosan and Cyclodextrin Polymer for the Prolonged Release of Triclosan.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

Lavandula pedunculata (Mill.) Cav. Aqueous Extract Antibacterial Activity Improved by the Addition of Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl and Origanum compactum Benth.

Lavender aqueous extracts are widely used in the Moroccan traditional medicine for their antibacterial properties. However, previous research have generally focused on investigating the antibacterial activity of lavender essential oils. The aim of this study is to evaluate the antibacterial activity of the Moroccan Lavandula pedunculata (Mill.) Cav. aqueous extract, alone, as well as in combination with extracts of other plant species known for their antibacterial activity: Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl. and Origanum compactum Benth. We have tested the antibacterial activity of L. pedunculata, S. rosmarinus, S. lavandulifolia and O. compactum aqueous extracts individually and in combination against 34 strains using the agar dilution method. The combination effect was evaluated using the fractional inhibitory concentration (FIC). Polyphenol and tannin contents were determined using Folin-Ciocalteu reagent, and then some phenolic compounds were identified using UHPLC-MS. All the extracts displayed a large spectrum of antibacterial activity, especially against staphylococci, streptococci, Mycobacterium smegmatis and Proteus mirabilis. The minimum inhibitory concentration (MIC) values reached 0.15 ± 0.00 mg/mL for Staphylococcus warneri tested with S. lavandulifolia and 0.20 ± 0.07 mg/mL for Staphylococcus epidermidis tested with L. pedunculata or S. rosmarinus. Association of the L. pedunculata extract with S. rosmarinus, S. lavandulifolia and O. compactum showed synergistic effects (FIC ≤ 1). Moreover, the association of L. pedunculata with S. lavandulifolia was active against most of the Gram-negative strains resistant to the individual extracts. Determination of polyphenol and tannin contents showed the richness of the studied plants in these compounds. Additionally, chromatographic analysis demonstrated the high presence of rosmarinic acid in all the studied plant extracts. To our knowledge, this is the first study that shows the enhancing effect of the antibacterial activity of L. pedunculata aqueous extract combined with S. rosmarinus, S. lavandulifolia and O. compactum. These results confirm the effectiveness of the plant mixtures commonly used by traditional healers in Morocco and suggest that L. pedunculata might be used as an antibacterial agent either alone or, more efficiently, in combination with S. rosmarinus, S. lavandulifolia and O. compactum.

Electrospun Filtering Membrane Designed as Component of Self-Decontaminating Protective Masks.

The 2019 coronavirus outbreak and worsening air pollution have triggered the search for manufacturing effective protective masks preventing both particulate matter and biohazard absorption through the respiratory tract. Therefore, the design of advanced filtering textiles combining efficient physical barrier properties with antimicrobial properties is more newsworthy than ever. The objective of this work was to produce a filtering electrospun membrane incorporating a biocidal agent that would offer both optimal filtration efficiency and fast deactivation of entrapped viruses and bacteria. After the eco-friendly electrospinning process, polyvinyl alcohol (PVA) nanofibers were stabilized by crosslinking with 1,2,3,4-butanetetracarboxylic acid (BTCA). To compensate their low mechanical properties, nanofiber membranes with variable grammages were directly electrospun on a meltblown polypropylene (PP) support of 30 g/m2. The results demonstrated that nanofibers supported on PP with a grammage of around only 2 g/m2 presented the best compromise between filtration efficiencies of PM0.3, PM0.5, and PM3.0 and the pressure drop. The filtering electrospun membranes loaded with benzalkonium chloride (ADBAC) as a biocidal agent were successfully tested against E. coli and S. aureus and against human coronavirus strain HCoV-229E. This new biocidal filter based on electrospun nanofibers supported on PP nonwoven fabric could be a promising solution for personal and collective protection in a pandemic context.

How Adding Chlorhexidine or Metallic Nanoparticles Affects the Antimicrobial Performance of Calcium Hydroxide Paste as an Intracanal Medication: An In Vitro Study.

The aim of our study was to explore the potential value of metallic (Ag, Cu, and Zn) salts, polymer/metallic nanoparticles, and chlorhexidine (CHX) for improving the antimicrobial activity of calcium hydroxide (CH) against E. faecalis and C. albicans, associated with persistent endodontic infections. A first screening was performed by determining minimum inhibitory/bactericidal concentrations (MIC/MBC). Antimicrobial activity of the CH paste mixed with metallic salts, chitosan or cyclodextrin polymer metallic nanoparticles was compared to the antimicrobial activity of CH paste alone and CH + CHX using a time-kill kinetics assay. The effect of the antimicrobials on the rheological and the key mechanical properties were also examined. Copper and zinc were discarded because of their MIC/MBC values and silver because of its kill time curve profile. Except for a slower setting time after 24 h and a higher weight loss after 1 week of incubation, the mechanical behavior of the CH paste was unaffected by the addition of CHX. Polymeric/metallic nanoparticles failed to potentiate the antimicrobial effect of CH. By contrast, CHX increased this effect and thus could help eradicate E. faecalis associated with persistent root canal infections without altering the desired key physical properties of the CH paste.

Carriage of Multidrug-Resistant Bacteria in Healthy People: Recognition of Several Risk Groups.

The increase in multidrug-resistant (MDR) bacteria in hospitalized people and the hospital environment has been thoroughly documented. In contrast, little is known about their presence in the community. However, increasing evidence is showing a high level of carriage in people without infectious signs. Colonized people can later develop infections due to MDR bacteria and may be able to transmit them to susceptible people (the number of which is increasing worldwide), for example, people with comorbidities such as diabetes, cancer, or inflammatory diseases and those in extreme age groups. Risk factors for the acquisition of MDR bacteria are as follows: (1) residence or travel in countries with high levels of MDR bacteria; (2) occupational risks such as health workers or people with close contact with animals (farmers, veterinarians) who frequently use antibiotics; and (3) comorbidities. Eradication is rather difficult and, thus far, has not shown clear-cut results. Preventive measures will be important in the future with a reinforcement of hygienic measures not only in the hospital, but also in the community.

Adherent-Invasive and Non-Invasive Escherichia coli Isolates Differ in Their Effects on Caenorhabditis elegans' Lifespan.

The adherent-invasive Escherichia coli (AIEC) pathotype has been implicated in the pathogenesis of inflammatory bowel diseases in general and in Crohn's disease (CD) in particular. AIEC strains are primarily characterized by their ability to adhere to and invade intestinal epithelial cells. However, the genetic and phenotypic features of AIEC isolates vary greatly as a function of the strain's clonality, host factors, and the gut microenvironment. It is thus essential to identify the determinants of AIEC pathogenicity and understand their role in intestinal epithelial barrier dysfunction and inflammation. We reasoned that soil nematode Caenorhabditis elegans (a simple but powerful model of host-bacterium interactions) could be used to study the virulence of AIEC vs. non- AIEC E. coli strains. Indeed, we found that the colonization of C. elegans (strain N2) by E. coli impacted survival in a strain-specific manner. Moreover, the AIEC strains' ability to invade cells in vitro was linked to the median lifespan in C. elegans (strain PX627). However, neither the E. coli intrinsic invasiveness (i.e., the fact for an individual strain to be characterized as invasive or not) nor AIEC's virulence levels (i.e., the intensity of invasion, established in % from the infectious inoculum) in intestinal epithelial cells was correlated with C. elegans' lifespan in the killing assay. Nevertheless, AIEC longevity of C. elegans might be a relevant model for screening anti-adhesion drugs and anti-invasive probiotics.

In Vitro Microbiological and Drug Release of Silver/Ibuprofen Loaded Wound Dressing Designed for the Treatment of Chronically Infected Painful Wounds.

This study consisted of developing a dressing loaded with silver (Ag) and ibuprofen (IBU) that provides a dual therapy, antibacterial and antalgic, intended for infected painful wounds. Therefore, non-woven polyethyleneterephtalate (PET) textiles nonwovens were pre-treated by cyclodextrin crosslinked with citric acid by a pad/dry/cure process. Then, textiles were impregnated in silver solution followed by a thermal treatment and were then coated by Layer-by-Layer (L-b-L) deposition of a polyelectrolyte multilayer (PEM) system consisting of anionic water-soluble poly(betacyclodextrin citrate) (PCD) and cationic chitosan. Finally, ibuprofen lysinate (IBU-L) was loaded on the PEM coating. We demonstrated the complexation of IBU with native ßCD and PCD by phase solubility diagram and 1H NMR. PEM system allowed complete IBU-L release in 6 h in PBS pH 7.4 batch (USP IV). On the other hand, microbiological tests demonstrated that loaded silver induced bacterial reduction of 4 Log10 against S. aureus and E. coli and tests revealed that ibuprofen lysinate loading did not interfere with the antibacterial properties of the dressing.

Injection-molded capsule bodies and caps based on polymer blends for controlled drug delivery.

A variety of polymer:polymer blends was used to prepare hot melt extrudates and empty capsules (bodies and caps) by injection-molding using a benchtop extruder (Babyplast). KollidonSR:inulin and Carbothane:inulin blends were investigated. The impact of the blend ratio on the water uptake and dry mass loss kinetics upon exposure to 0.1 MHCl, phosphate buffer pH6.8 and culture medium optionally inoculated with fecal samples from Inflammatory Bowel Disease (IBD) patients were studied. Hot melt extrudates were loaded with up to 60% theophylline, capsules were filled with drug powder. Increasing the inulin content led to increased water uptake and dry mass loss rates, resulting in accelerated drug release from the dosage forms, irrespective of the type of polymer blend. This can be attributed to the higher hydrophilicity/water-solubility of this polymer compared to KollidonSR and Carbothane. Interestingly, the presence of fecal samples in culture medium increased the water uptake and dry mass loss of hot melt extrudates to a certain extent, suggesting partial system degradation by bacterial enzymes. However, these phenomena did not translate into any noteworthy impact of the presence of colonic bacteria on theophylline release from the investigated extrudates or capsules. Hence, drug release can be expected to be independent of the location "small intestine vs. colon" from these dosage forms, which can be advantageous for long term release throughout the entire gastro intestinal tract.

Antibacterial and antioxidant activities of a novel enol ether nor-sesquiterpene isolated from Myrtus nivellei Batt. & Trab.

Myrtus nivellei is a plant traditionally used to treat diseases including infection of microbial origin. Several M. nivellei Batt. & Trab. extracts (dichloromethane, methanol and ethanol/water) were screened for their activity against 36 microorganisms, including strains resistant to antibiotics. These extracts inhibited on average 15 bacteria strains with minimum inhibition concentrations (MICs) ranging from 0.07 to 1.20 mg/mL. Bioassay guided fractionation was carried out with bioautography on TLC plates using four pathogenic bacteria strains, and following chromatographies (CPC and HPLC) led to the isolation of two novel enol ether nor-cadinane sesquiterpenes from the dichloromethane extract. The major compound (1) showed a strong antibacterial activity. Minimal inhibition concentration and minimal bactericidal concentration (MBC) values were determined against four bacteria: Acinetobacter baumanii, Stenotrophomonas maltophilia, Yersinia pseudotuberculosis and Staphylococcus lugdunensis. The best activity was observed against Acinetobacter baumanii with a MIC value of 9.7 µg/mL. This novel compound was also very active against a Staphylococcus aureus strain resistant to amoxicillin (MIC 19.5 µg/mL). In addition, compound 1 showed a very high antioxidant activity with both DPPH and metal chelate methods.

Assessment of Pb(II), Cd(II), and Al(III) Removal Capacity of Bacteria from Food and Gut Ecological Niches: Insights into Biodiversity to Limit Intestinal Biodisponibility of Toxic Metals.

Toxic metals (such as lead, cadmium, and, to a lesser extent, aluminum) are detrimental to health when ingested in food or water or when inhaled. By interacting with heavy metals, gut and food-derived microbes can actively and/or passively modulate (by adsorption and/or sequestration) the bioavailability of these toxins inside the gut. This "intestinal bioremediation" involves the selection of safe microbes specifically able to immobilize metals. We used inductively coupled plasma mass spectrometry to investigate the in vitro ability of 225 bacteria to remove the potentially harmful trace elements lead, cadmium, and aluminum. Interspecies and intraspecies comparisons were performed among the Firmicutes (mostly lactic acid bacteria, including Lactobacillus spp., with some Lactococcus, Pediococcus, and Carnobacterium representatives), Actinobacteria, and Proteobacteria. The removal of a mixture of lead and cadmium was also investigated. Although the objective of the study was not to elucidate the mechanisms of heavy metal removal for each strain and each metal, we nevertheless identified promising candidate bacteria as probiotics for the intestinal bioremediation of Pb(II) and Cd(II).

Adherent invasive Escherichia coli (AIEC) strain LF82, but not Candida albicans, plays a profibrogenic role in the intestine.

BACKGROUND: Intestinal fibrosis is a frequent complication of Crohn's disease. However, the factors that cause chronicity and promote fibrogenesis are not yet understood. AIMS: In the present study, we evaluated the profibrotic effects of adherent-invasive Escherichia coli (AIEC) LF82 strain and Candida albicans in the gut. METHODS: Colonic fibrosis was induced in C57BL/6 mice by administration of three cycles of 2.5% (w/v) dextran sulfate sodium (DSS) for 5 weeks. LF82 and C. albicans were administered orally once at the start of each week or each cycle, respectively. Expression of markers of myofibroblast activation was determined in TGF-ß1-stimulated human intestinal epithelial cells (IECs). RESULTS: LF82 administration exacerbated fibrosis in DSS-treated mice, revealed by increased colonic collagen deposition and expression of the profibrotic genes Col1a1, Col3a1, Fn1 and Vim. This was accompanied by enhanced gene expression of proinflammatory cytokines and chemokines, as well as more recruited inflammatory cells into the intestine. LF82 also potentiated TGF-ß1-stimulated epithelial-mesenchymal transition and myofibroblast activation in IECs, by further inducing gene expression of the main mesenchymal cell markers FN1 and VIM and downregulating the IEC marker OCLN. Proinflammatory cytokines were overexpressed with LF82 in TGF-ß1-stimulated IECs. Conversely, C. albicans did not affect intestinal fibrosis progression in DSS-treated mice or myofibroblast activation in TGF-ß1-stimulated IECs. CONCLUSIONS: These results demonstrate that AIEC strain LF82, but not C. albicans, may play a major profibrogenic role in the gut.

MeJA Elicitation of Chicory Hairy Roots Promotes Efficient Increase of 3,5-diCQA Accumulation, a Potent Antioxidant and Antibacterial Molecule.

Cichorium intybus L. (Asteraceae) is an important industrial crop, as well as a medicinal plant which produces some bioactive compounds implicated in various biological effects with potential applications in human health. Particularly, roots produce hydroxycinnamic acids like 5-caffeoyquinic acid and 3,5-dicaffeoylquinic acid (di-CQA). The present investigation relates to the use of methyl jasmonate for enhancing phenolic compounds accumulation and production in hairy root cultures of C. intybus. Elicitated hairy root growth rate increased 13.3 times compared with the initial inoculum in a period of 14 days and di-CQA production represented about 12% of DW. The elicitation has also promoted the production of tricaffeoylquinic acid never described in the chicory roots and identified as 3,4,5-tricaffeoyquinic acid by means of nuclear magnetic resonance. Our study confirmed the strong anti-oxidant effect of di-CQA. Our results also confirmed globally a selectivity of action of di-CQA against Gram-positive bacteria, in particular against some strains of Staphylococcus and Streptococcus. However, a non-negligible antibacterial activity of di-CQA against Pseudomonas aeruginosa was also underlined (MIC = 0.156 mg.mL-1 against some P. aeruginosa strains). The influence of di-CQA has been explored to evaluate its impact on the physiology of P. aeruginosa. Di-CQA showed no effect on the biofilm formation and the production of extracellular pyocyanin. However, it demonstrated an effect on virulence through the production of pyoverdine with a dose-dependent manner by more than 7-fold when treated at a concentration of 128 µg·mL-1, thus suggesting a link between di-CQA and iron sequestration. This study shows that elicitated hairy root cultures of chicory can be developed for the production of di-CQA, a secondary metabolite with high antibacterial potential.

Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening.

Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and ß-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.