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Flavonoids possess different interesting biological properties, including antibacterial, antiviral, anti-inflammatory and antioxidant activities. However, unfortunately, these molecules present different bottlenecks, such as low aqueous solubility, photo and oxidative degradability, high first-pass effect, poor intestinal absorption and, hence, low systemic bioavailability. A variety of delivery systems have been developed to circumvent these drawbacks, and among them, in this work niosomes have been selected to encapsulate the hepatoprotective natural flavonoid quercetin. The aim of this study was to prepare nanosized quercetin-loaded niosomes, formulated with different monolaurate sugar esters (i.e., sorbitan C12; glucose C12; trehalose C12; sucrose C12) that act as non-ionic surfactants and with cholesterol as stabilizer (1:1 and 2:1 ratio). Niosomes were characterized under the physicochemical, thermal and morphological points of view. Moreover, after the analyses of the in vitro biocompatibility and the drug-release profile, the hepatoprotective activity of the selected niosomes was evaluated in vivo, using the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Furthermore, the levels of glutathione and glutathione peroxidase (GSH and GPX) were measured. Based on results, the best formulation selected was glucose laurate/cholesterol at molar ratio of 1:1, presenting spherical shape and a particle size (PS) of 161 ± 4.6 nm, with a drug encapsulation efficiency (EE%) as high as 83.6 ± 3.7% and sustained quercetin release. These niosomes showed higher hepatoprotective effect compared to free quercetin in vivo, measuring serum biomarker enzymes (i.e., alanine and aspartate transaminases (ALT and AST)) and serum biochemical parameters (i.e., alkaline phosphatase (ALP) and total proteins), while following the histopathological investigation. This study confirms the ability of quercetin loaded niosomes to reverse CCl4 intoxication and to carry out an antioxidant effect.

This study was conducted to investigate the impact of glycerol monolaurate (GML) on performance, immunity, intestinal barrier, and cecal microbiota in broiler chicks. A total of 360 one-day-old broilers (Arbor Acres) with an average weight of 45.7 g were randomly allocated to five dietary groups as follows: basal diet and basal diets complemented with 300, 600, 900, or 1200 mg/kg GML. Samples were collected at 7 and 14 days of age. Results revealed that feed intake increased ( P < 0.05) after 900 and 1200 mg/kg GML were administered during the entire 14-day experiment period. Dietary GML decreased ( P < 0.05) crypt depth and increased the villus height-to-crypt depth ratio of the jejunum. In the serum and jejunum, supplementation with more than 600 mg/kg GML reduced ( P < 0.05) interleukin-1β, tumor necrosis factor-α, and malondialdehyde levels and increased ( P < 0.05) the levels of immunoglobulin G, jejunal mucin 2, total antioxidant capacity, and total superoxide dismutase. GML down-regulate ( P < 0.05) jejunal interleukin-1β and interferon- γ expression and increased ( P < 0.05) the mRNA level of zonula occludens 1 and occludin. A reduced ( P < 0.05) expression of toll-like receptor 4 and nuclear factor kappa-B was shown in GML-treated groups. In addition, GML modulated the composition of the cecal microbiota of the broilers, improved ( P < 0.05) microbial diversity, and increased ( P < 0.05) the abundance of butyrate-producing bacteria. Spearman’s correlation analysis revealed that the genera Barnesiella , Coprobacter , Lachnospiraceae , Faecalibacterium , Bacteroides , Odoriacter , and Parabacteroides were related to inflammation and intestinal integrity. In conclusion, GML ameliorated intestinal morphology and barrier function in broiler chicks probably by regulating intestinal immune and antioxidant balance, as well as intestinal microbiota.

The objective of this study was to determine the in vitro antimicrobial activity of several organic acids and their derivatives against Gram-positive (G+) and Gram-negative (G−) bacteria. Butyric acid, valeric acid, monopropionin, monobutyrin, valerate glycerides, monolaurin, sodium formate, and ProPhorce—a mixture of sodium formate and formic acid (40:60 w/v)—were tested at 8 to 16 concentrations from 10 to 50,000 mg/L. The tested bacteria included G− bacteria (Escherichia coli, Salmonella enterica Typhimurium, and Campylobacter jejuni) and G+ bacteria (Enterococcus faecalis, Clostridium perfringens, Streptococcus pneumoniae, and Streptococcus suis). Antimicrobial activity was expressed as minimum inhibitory concentration (MIC) of tested compounds that prevented growth of tested bacteria in treated culture broth. The MICs of butyric acid, valeric acid, and ProPhorce varied among bacterial strains with the lowest MIC of 500–1000 mg/L on two strains of Campylobacter. Sodium formate at highest tested concentrations (20,000 mg/L) did not inhibit the growth of Escherichia coli, Salmonella Typhimurium, and Enterococcus faecalis, but sodium formate inhibited the growth of other tested bacteria with MIC values from 2000 to 18,800 mg/L. The MIC values of valerate glycerides, monolaurin, and monobutyrin ranged from 2500 to 15,000 mg/L in the majority of bacterial strains. Monopropionin did not inhibit the growth of all tested bacteria, with the exception that the MIC of monopropionin was 11,300 mg/L on Clostridia perfringens. Monolaurin strongly inhibited G+ bacteria, with the MIC value of 10 mg/L against Streptococcus pneumoniae. The MIC tests indicated that organic acids and their derivatives exhibit promising antimicrobial effects in vitro against G− and G+ bacteria that are resistant to antimicrobial drugs. The acid forms had stronger in vitro antimicrobial activities than ester forms, except that the medium chain fatty acid ester monolaurin exhibited strong inhibitory effects on G+ bacteria.

Porcine epidemic diarrhea virus (PEDV) has reemerged as the main pathogen of piglets due to its high mutation feature. Monolaurin (ML) is a natural compound with a wide range of antibacterial and antiviral activities. However, the role of ML in PEDV infection is still unknown. This study aimed to evaluate the effect of ML on the growth performance, intestinal function, virus replication and cytokine response in piglets infected with PEDV, and to reveal the mechanism through proteomics analysis. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 days before PEDV infection. Results showed that although there was no significant effect on the growth performance of piglets, ML administration alleviated the diarrhea caused by PEDV infection. ML administration promoted the recovery of intestinal villi, thereby improving intestinal function. Meanwhile, PEDV replication was significantly inhibited, and PEDV-induced expression of IL-6 and IL-8 were decreased with ML administration. Proteomics analyses showed that 38 proteins were differentially expressed between PEDV and ML+PEDV groups and were significantly enriched in the interferon-related pathways. This suggests ML could promote the restoration of homeostasis by regulating the interferon pathway. Overall, the present study demonstrated ML could confer a protective effect against PEDV infection in piglets and may be developed as a drug or feed additive to prevent and control PEDV disease.

Imaging lipid organization in cell membranes requires advanced fluorescent probes. Here, we show that a recently synthesized push-pull pyrene (PA), similarly to popular probe Laurdan, changes the emission maximum as a function of lipid order, but outperforms it by spectroscopic properties. In addition to red-shifted absorption compatible with common 405 nm diode laser, PA shows higher brightness and much higher photostability than Laurdan in apolar membrane environments. Moreover, PA is compatible with two-photon excitation at wavelengths >800 nm, which was successfully used for ratiometric imaging of coexisting liquid ordered and disordered phases in giant unilamellar vesicles. Fluorescence confocal microscopy in Hela cells revealed that PA efficiently stains the plasma membrane and the intracellular membranes at >20-fold lower concentrations, as compared to Laurdan. Finally, ratiometric imaging using PA reveals variation of lipid order within different cellular compartments: plasma membranes are close to liquid ordered phase of model membranes composed of sphingomyelin and cholesterol, while intracellular membranes are much less ordered, matching well membranes composed of unsaturated phospholipids without cholesterol. These differences in the lipid order were confirmed by fluorescence lifetime imaging (FLIM) at the blue edge of PA emission band. PA probe constitutes thus a new powerful tool for biomembrane research.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins that contribute to lateral heterogeneity in eukaryotic membranes. Separation of artificial membranes into liquid-ordered (Lo) and liquid-disordered phases is regarded as a common model for this compartmentalization. However, tight lipid packing in Lo phases seems to conflict with efficient partitioning of raft-associated transmembrane (TM) proteins. To assess membrane order as a component of raft organization, we performed fluorescence spectroscopy and microscopy with the membrane probes Laurdan and C-laurdan. First, we assessed lipid packing in model membranes of various compositions and found cholesterol and acyl chain dependence of membrane order. Then we probed cell membranes by using two novel systems that exhibit inducible phase separation: giant plasma membrane vesicles [Baumgart et al. (2007) Proc Natl Acad Sci USA 104:3165-3170] and plasma membrane spheres. Notably, only the latter support selective inclusion of raft TM proteins with the ganglioside GM1 into one phase. We measured comparable small differences in order between the separated phases of both biomembranes. Lateral packing in the ordered phase of giant plasma membrane vesicles resembled the Lo domain of model membranes, whereas the GM1 phase in plasma membrane spheres exhibited considerably lower order, consistent with different partitioning of lipid and TM protein markers. Thus, lipid-mediated coalescence of the GM1 raft domain seems to be distinct from the formation of a Lo phase, suggesting additional interactions between proteins and lipids to be effective.

Cellular membranes are heterogeneous in composition, and the prevailing theory holds that the structures responsible for this heterogeneity in vivo are small structures (10-200 nm), sterol- and sphingolipid-enriched, of different sizes, highly dynamic denominated rafts. Rafts are postulated to be platforms, which by sequestering different membrane components can compartmentalize cellular processes and regulate signaling pathways. Despite an enormous effort in this area, the existence of these domains is still under debate due to the characteristics of the structures itself: small in size and highly mobile, which from the technical point of view implies using techniques with high spatial and temporal resolution. In this report we measured rapid fluctuations of the normalized ratio of the emission intensity at two wavelengths of Laurdan, a membrane fluorescent dye sensitive to local membrane packing. We observed generalized polarization fluctuations in the plasma membrane of intact rabbit erythrocytes and Chinese hamster ovary cells that can be explained by the existence of tightly packed micro-domains moving in a more fluid background phase. These structures, which display different lipid packing, have different sizes; they are found in the same cell and in the entire cell population. The small size and characteristic high lipid packing indicate that these micro-domains have properties that have been proposed for lipid rafts.

A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive and Gram-negative bacteria. GML protected against high-dose SIV infection and reduced inflammation, which can exacerbate disease, during infection. We found that GML inhibits HIV-1 and other human-pathogenic viruses (yellow fever virus, mumps virus, and Zika virus), broadening its antimicrobial range. Because GML targets diverse infectious pathogens, GML may be an effective agent against the broad range of sexually transmitted pathogens. Further, our data show that reutericyclin, a GML analog expressed by some lactobacillus species, also inhibits HIV-1 replication and thus may contribute to the protective effect of Lactobacillus in HIV-1 transmission. The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin, glycerol monolaurate (GML), against microbial pathogens. Previous studies using a macaque vaginal simian immunodeficiency virus (SIV) transmission model demonstrated that GML reduces transmission and alters immune responses to infection in vitro . Previous studies showed that structural analogues of GML negatively impact other enveloped viruses. We sought to expand understanding of how GML inhibits HIV-1 and other enveloped viruses and show that GML restricts HIV-1 entry post-CD4 engagement at the step of coreceptor binding. Further, HIV-1 and yellow fever virus (YFV) particles were more sensitive to GML interference than particles “matured” by proteolytic processing. We show that high-pressure-liquid-chromatography (HPLC)-purified reutericyclin and reutericyclin secreted by Lactobacillus inhibit HIV-1. These data emphasize the importance and protective nature of the normal vaginal flora during viral infections and provide insights into the antiviral mechanism of GML during HIV-1 infection and, more broadly, to other enveloped viruses. IMPORTANCE A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive and Gram-negative bacteria. GML protected against high-dose SIV infection and reduced inflammation, which can exacerbate disease, during infection. We found that GML inhibits HIV-1 and other human-pathogenic viruses (yellow fever virus, mumps virus, and Zika virus), broadening its antimicrobial range. Because GML targets diverse infectious pathogens, GML may be an effective agent against the broad range of sexually transmitted pathogens. Further, our data show that reutericyclin, a GML analog expressed by some lactobacillus species, also inhibits HIV-1 replication and thus may contribute to the protective effect of Lactobacillus in HIV-1 transmission.

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.83 mL packed‐bed reactor, followed by its application as a biocatalyst for the synthesis of hexyl laurate in an integrated process. Initially, the percolation of a solution containing 5 mg of TLL at 25 °C and flows ranging from 1.767 to 0.074 mL min−1 was investigated, where at the lowest flow rate tested (residence time of 2 h), it was possible to obtain an immobilized derivative with hydrolytic activity of 504.7 U g−1 and 31.7 % of recovered activity. Subsequent studies of treatment with n‐hexane, as well as the effect of temperature on the immobilization process, were able to improve the activities of the final biocatalyst BM‐TLLF, achieving a final hydrolysis activity of 7023 U g−1 and esterification activity of 430 U ⋅ g−1 against 142 U g−1 and 113.5 U g−1 respectively presented by the commercial TLIM biocatalyst. Desorption studies showed that the TL IM has 18 mg of protein per gram of support, compared to 4.92 mg presented by BM‐TLL. Both biocatalysts were applied to synthesize hexyl laurate, achieving 98 % conversion at 40 °C within 2 h. Notably, BM‐TLLF displayed exceptional recyclability, maintaining catalytic efficiency over 12 cycles. This reflects a productivity of 180 mg of product ⋅ h−1 U−1 of the enzyme, surpassing 46 mg h−1 U−1 obtained for TLIM. These results demonstrate the efficacy of continuous flow technology in creating a competitive and integrated process offering an exciting alternative for the valorization of residual lignocellulosic biomass. In this work, the reuse of residual babassu mesocarp as a support for the immobilization of TLL lipase in bed reactors was investigated, with subsequent integration in the synthesis of hexyl laurate, generating competitive biocatalysts with high esterification activity and generating conversions of over 95 % in esters in just 120 minutes in comparison to batch reactors.

Skin and surgical infections due to Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii are causes of patient morbidity and increased healthcare costs. These organisms grow planktonically and as biofilms, and many strains exhibit antibiotic resistance. This study examines the antibacterial and anti-biofilm activity of glycerol monolaurate (GML), as solubilized in a non-aqueous vehicle (5% GML Gel), as a novel, broadly-active topical antimicrobial. The FDA has designated GML as generally recognized as safe for human use, and the compound is commonly used in the cosmetic and food industries. In vitro, bacterial strains in broths and biofilms were exposed to GML Gel, and effects on bacterial colony-forming units (CFUs) were assessed. In vivo,subcutaneous incisions were made in New Zealand white rabbits; the incisions were closed with four sutures. Bacterial strains were painted onto the incision sites, and then GML Gel or placebo was liberally applied to cover the sites completely. Rabbits were allowed to awaken and were examined for CFUs as a function of exposure time. In vitro, GML Gel was bactericidal for all broth culture and biofilm organisms in <1 hour and <4 hour, respectively; no CFUs were detected after the entire 24 h test period. In vivo, GML Gel inhibited bacterial growth in the surgical incision sites, compared to no growth inhibition in controls. GML Gel significantly reduced inflammation, as viewed by lack of redness in and below the incision sites. Our findings suggest that 5% GML Gel is useful as a potent topical antibacterial and anti-inflammatory agent for prevention of infections.