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Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections. Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by (AgNP ) in combination with simvastatin against reference and multidrug-resistant bacterial strains. Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL against MRSA. AgNP with a size of 77.68± 33.95 nm and zeta potential -34.6 ± 12.7 mV showed an MIC of 0.212 mg mL against including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNP combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNP demonstrated antibacterial activity against producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNP and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA. Our results indicate that the combination of AgNP and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNP are required, with the same antibacterial activity.

Several studies have tested antimicrobial activity of combinations of honey and various substances. In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM). The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v −1 ) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined. This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains.

Nitric oxide (NO) is a small but powerful molecule. It is involved in several biological pathways such as vasodilation, wound healing and toxicity towards pathogens. At high concentrations, NO has a toxicity towards bacteria, virus and fungi which has a great biomedical potential. However, NO has a small half-life of just a few seconds and this hazards its clinical application. In this scenario, the combination of nanotechnology with NO donors can create new strategies to load and deliver NO. Polymeric nanomaterial intrinsically have advantages such as low toxicity, biodegradability and low-cost. In this study, we used chemically modified chitosan (CS) to prepare nanoparticles capable of loading and releasing NO with antibacterial activity. CS was chemically modified to add a thiol group (-SH) to its structure. This modification was performed by the reaction with thioglycolic acid (TGA) in the presence of a carbodiimide (EDC). The thiol groups in CS structure serve a double function: create an anchorage site for NO and increase polymer mucoadesivity. The synthesis of thiolated chitosan nanoparticles (TCS NP) occurred by ionotropic gelation method using sodium tripolyphosphate (TPP) as counter ion. The NO donor precursor molecule, mercaptosuccinic acid (MSA), was encapsulated into TCS NP to increase loading capacity of NO. To identify the best paraments of the synthesis we used the ratios 1:3, 1:4, 1:5, 1:6 and 1:7 for TCS:TPP. TCS NPs were characterized by dynamic light scattering (DLS), microscopy electron transmission (MET) and nanoparticle tracking analysis (NTA). The release of NO was characterized by a kinetic using Uv-vis spectroscopy. Finally, the antibacterial potential was evaluated by minimum inhibitory concentration (MIC) assay against Staphylococcus aureus, Streptococcus mutans and Escherichia coli strains. The ratio 1:5 showed the most adequate size parameters and the other analysis were performed using it. The hydrodynamic size was found to be 113.0 ± 1.6 nm, PDI of 0.292 ± 0.035 and zeta potential of 27.1 ± 0.9. The MET images indicated small and spherical nanoparticles. The kinetic profiles showed a linear release of NO reaching the 100% after 150 min. The antibacterial effect was tested for E. coli, S. aureus and S. mutans. The MIC values was 50 µg mL for NO-CS NP, this result was 50% lower compared to TCS NPs for S. mutans and E. coli. The TCS NP has suitable properties for the biomedical field with potential for antibacterial application.

Plants contain numerous constituents and are valuable sources of new biologically active molecules. Avocado (Persea americana Mill.) is cultivated and used as food in most tropical and subtropical countries. Its high nutritional value and biological activities, as antioxidant, antimicrobial and analgesic properties, have been thoroughly investigated. Interest in plant extracts with antimicrobial properties has increased as a result of the indiscriminate use of antibiotics, leading to the emergence of resistant bacterial strains. Among bacterial species with clinical importance to multiple hosts, Streptococcus agalactiae is outstanding, as it can cause infections especially in humans, fish and cattle. The current study aimed to evaluate the antimicrobial activity of two extracts (ethanol and dichloromethane) from avocado seeds, ‘Margarida’ variety, against isolates of S. agalactiae. Extracts were diluted in ethanol / water (1:1) at a concentration of 100 mg/mL. Antimicrobial activity was tested by the disk diffusion method (antibiogram) against isolates of S. agalactiae of human and fish origin.The ethanol extract showed antimicrobial activity only for some isolates of S. agalactiae of human origin. The dichloromethane extract showed activity against all isolates of S. agalactiae of both origins. A comparison of the results obtained with dichloromethane extract from isolates of S. agalactiae of human or fish origin demonstrated the existence of phenotypic variability among isolates from the same host. However, when comparing measurements obtained in each of the groups, they were statistically similar, showing a lack of interpopulation variability. Thus, it can be verified that the resistance profile of isolates of S. agalactiae was independent of host origin and typical of the species.

The nanocarrier was synthesized by nanoprecipitation, using poly( epsilon -caprolactone) (PCL) as polymer, Tween 80 as surfactant and the biopolymer chitosan (CS) as a charge modification agent. Charge, size and morphology were analyzed by zeta potential, photo correlation spectroscopy (PCS), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Bactericidal assays were carried out using a resistant strain of Staphylococcus aureus, and the acute ecotoxicity tests were performed with Daphnia similis. The nanoparticle without CS (PCLnp) exhibited an average size of 200 nm and zeta potential of -4.28 mV, while the nanoparticle with 0.04% (w/v) of CS (CS_PCLnp) had 250 nm and +21.3 mV. Both were stables for at least 30 days. 200 mu g mL super(-1) violacein was encapsulated in CS_PCLnp, which was dissolved in the polymer matrix, a shown by DSC analysis. The minimal inhibitory concentration against S. aureus of CS_PCLnp-vio was 25 mu mol L super(-1), while for free violacein it was > 25 mu mol L super(-1). Nanoparticles exhibited an EC50 between 0.3 - 1.1 mu mol L super(-1) with Daphnia, while free violacein was around 3.3 - 5.0 mu mol L super(-1). Thus, it was possible to control the charge of the nanoparticles, without extreme changes in size and that it is possible also to encapsulate a powerful antibactericidal compound such as violacein in nanoparticle.

The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was investigated regarding its prebiotic activity on enteropathogenic Escherichia coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC strains. Then MOS was supplied once a day, in water for 20 days. Immunological (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and bacteriological variables (PCR detection of the eae gene of EPEC recovered from stool culture), as well as occurrence of diarrhea were evaluated. All strains caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E. coli isolated from stool culture of all infected animals had the eae gene. There was no significant difference among groups as to number of blood cells in the hemogram and IgA and IgG production. MOS was effective in recovering of EPEC-infected dogs since prebiotic-treated animals recovered more rapidly from infection than untreated ones (p < 0.05). This is an important finding since diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for humans and other animals with diarrhea can be an alternative for the treatment and prophylaxis of EPEC infections.

Streptococcus agalactiae (group B streptococci (GBS)) is an important infections agent in newborns associated with maternal vaginal colonization. Intrapartum antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant reduction in the incidence of early neonatal infection in various geographic regions. However, this strategy may lead to resistance selecting among GBS, indicating the need for new alternatives to prevent bacterial transmission and even to treat GBS infections. This study reported for the first time the effect of eugenol on GBS isolated from colonized women, alone and in combination with silver nanoparticles produced by Fusarium oxysporum (AgNPbio). Eugenol showed a bactericidal effect against planktonic cells of all GBS strains, and this effect appeared to be time-dependent as judged by the time-kill curves and viability analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic activity, significantly reducing the minimum inhibitory concentration values of both compounds. Scanning and transmission electron microscopy revealed fragmented cells and changes in bacterial morphology after incubation with eugenol. In addition, eugenol inhibited the viability of sessile cells during biofilm formation and in mature biofilms. These results indicate the potential of eugenol as an alternative for controlling GBS infections.

Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age. In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4–5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673. Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081–0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090–0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy. Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.

We present the number densities and physical properties of the bright galaxies spectroscopically confirmed at z ∼ 7–14. Our sample is composed of 60 galaxies at zspec ∼ 7–14, including recently confirmed galaxies at zspec = 12.34–14.18 with JWST, as well as new confirmations at zspec = 6.583–7.643 with −24 < MUV < −21 mag using ALMA and Keck. Our JWST/NIRSpec observations have also revealed that very bright galaxy candidates at z ∼ 10–13 identified from ground-based telescope images before JWST are passive galaxies at z ∼ 3–4, emphasizing the necessity of strict screening and spectroscopy in the selection of the brightest galaxies at z > 10. The UV luminosity functions derived from these spectroscopic results are consistent with a double power-law function, showing tensions with theoretical models at the bright end. To understand the origin of the overabundance of bright galaxies, we investigate their morphologies using JWST/NIRCam high-resolution images obtained in various surveys, including PRIMER and COSMOS-Web. We find that ∼70% of the bright galaxies at z ∼ 7 exhibit clumpy morphologies with multiple subcomponents, suggesting merger-induced starburst activity, which is consistent with SED fitting results showing bursty star formation histories. At z ≳ 10, bright galaxies are classified into two types of galaxies: extended ones with weak high-ionization emission lines, and compact ones with strong high-ionization lines including N iv]λ1486, indicating that at least two different processes (e.g., merger-induced starburst and compact star formation/AGN) are shaping the physical properties of the brightest galaxies at z ≳ 10 and are responsible for their overabundance.