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The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-β-cyclodextrin (HP-β-CD). Compared with solubility of pure GML <80 μg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 μg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates. A Higuchi's A L -type phase-solubility diagram indicated the strong interaction between host and guest molecules with the formation of 1:1 GML/HP-β-CD complex and the stability constant at 6248 L/mol. Compared with pure GML, encapsulated GML at the same concentration can also show good antibacterial capabilities against S. aureus and E. coli in sterile water, and the effective preservative capabilities towards beef meatballs. The boosted enhancement in water-solubility of GML and the effective antibacterial capabilities endowed IC with potential in the application of food decontamination., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2023. Published by Elsevier Ltd.)

In this study, based on the discovery of thymol/glycerol monolaurate (GML) eutectic solvent, we studied the effect of GML as a multi-functional component (ripening inhibitor and antibacterial agent) on the formation, stability and antibacterial activity of eutectic nanoemulsions, and investigated the preservation of nanoemulsion in fresh pork. These results indicated that the formation of eutectic solvent was due to the hydrogen bonding between thymol and GML in the molten state. And eutectic nanoemulsions prepared with medium GML concentrations (20%, 40%, and 60%) of eutectic solvents as oil phases had small droplet diameters (<150 nm), exhibited sustained-release characteristics, and had excellent physicochemical stability. Moreover, the addition of GML enhanced the antibacterial activity of thymol nanoemulsion against S. aureus. as seen by their ability to inhibit affect formation more effectively. Treatment of fresh pork with optimized eutectic nanoemulsions (40% thymol/60% GML) extended its shelf life during refrigeration, which was mainly attributed to the ability of the encapsulated essential oil to inhibit microbial growth and lipid oxidation. These results provide a novel strategy to control Ostwald ripening and maintain the high antibacterial activity of thymol in nanoemulsion-based delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aquatic products are highly susceptible to spoilage, and preparing composite edible film with essential oil is an effective solution. In this study, composite edible films were prepared using perilla essential oil (PEO)-glycerol monolaurate emulsions incorporated with chitosan and nisin, and the film formulation was optimized by response surface methodology. These films were applied to ready-to-eat fish balls and evaluated over a period of 12 days. The films with the highest inhibition rate against Staphylococcus aureus were acquired using a polymer composition of 6 μL/mL PEO, 18.4 μg/mL glycerol monolaurate, 14.2 mg/mL chitosan, and 11.0 μg/mL nisin. The fish balls coated with the optimal edible film showed minimal changes in appearance during storage and significantly reduced total bacterial counts and total volatile basic nitrogen compared to the control groups. This work indicated that the composite edible films containing essential oils possess ideal properties as antimicrobial packaging materials for aquatic foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

To improve nutritional health, a low-salt (0.5 %) silver carp (Hypophthalmichthys molitrix) surimi gel with α-tocopherol, soybean oil, and glyceryl monostearate oleogel was fabricated and evaluated for textural qualities, lipid oxidation, and in-vitro digestion analysis. Based on the texture profile analysis, gel strength, water holding capacity (WHC), rheological, protein secondary structure, and microstructural examination, 5 % oleogel addition to low-salt surimi exhibited similar physicochemical properties to regular-salt surimi gels. By crosslinking myosin and filling protein network voids, the oleogel increased surimi gel density. Increasing oleogel content improved the physicochemical qualities of heat-induced surimi, causing protein aggregation during digestion and reducing digestibility. The presence of oleogel altered protein secondary structure, reducing α-helix content and increasing β-sheet and other structures, enhancing WHC and gel strength of low salt surimi. Adding oleogel improved the antioxidant activity of digestive solutions. This study will help understand myosin-oleogel interaction and the development of sustainable and nutritious surimi-based foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells (P < 0.05) without affecting cell viability (P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes (P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes (P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS (P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 (P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS (P < 0.05), as well as the phosphorylation of NF-κB p65 (P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Organic acids are widely used in foodstuffs to inhibit pathogen and spoiler growth. In this study, six organic acids (acetic, lactic, propionic, phenyllactic, caprylic, and lauric acid) and monolaurin were selected based on their physicochemical properties: their molecular structure (carbon chain length), their lipophilicity (logP), and their ability to dissociate in a liquid environment (pKa). The relation between these physicochemical properties and the inhibitory efficacy against B. weihenstephanensis KBAB4 growth was evaluated. After assessing the active form of these compounds against the strain (undissociated, dissociated or both forms), their MIC values were estimated in nutrient broth at pH 6.0 and 5.5 using two models (Lambert & Pearson, 2000; Luong, 1985). The use of two models highlighted the mode of action of an antibacterial compound in its environment, thanks to the additional estimation of the curve shape α or the Non-Inhibitory Concentration (NIC). The undissociated form of the tested acids is responsible for growth inhibition, except for lauric acid and monolaurin. Moreover, long-carbon chain acids have lower estimated MICs, compared to short-chain acids. Thus, the inhibitory efficacy of organic acids is strongly related to their carbon chain length and lipophilicity. Lipophilicity is the main mechanism of action of a membrane-active compound, it can be favored by long chain structure or high pKa in an acid environment like food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The advancement of the Penaeus vannamei industry in a sustainable manner necessitates the creation of eco-friendly and exceptionally effective feed additives. To achieve this, 720 similarly-sized juvenile shrimp (0.88 ± 0.02 g) were randomly divided into four groups in this study, with each group consisting of three replicates, each tank (400 L) containing 60 shrimp. Four experimental diets were formulated by adding 0, 500, 1000, and 1500 mg kg -1 glycerol monolaurate (GML) to the basal diet, and the feeding trial lasted for 42 days. Subsequently, a 72-h White Spot Syndrome Virus (WSSV) challenge test was conducted. Polynomial orthogonal contrasts analysis revealed that with the increase in the concentration of GML, those indicators related to growth, metabolism and immunity, exhibit linear or quadratic correlations (P < 0.05). The results indicate that the GML groups exhibited a significant improvement in the shrimp weight gain rate, specific growth rate, and a reduction in the feed conversion ratio (P < 0.05). Furthermore, the GML groups promoted the lipase activity and reduced lipid content of the shrimp, augmented the expression of triglyceride and fatty acid decomposition-related genes and lowered the levels of plasma triglycerides (P < 0.05). GML can also enhanced the humoral immunity of the shrimp by activating the Toll-like receptor and Immune deficiency immune pathways, improved the phagocytic capacity and antibacterial ability of shrimp hemocytes. The challenge test revealed that GML significantly reduced the mortality of the shrimp compared to control group. The 16S rRNA sequencing indicates that the GML group can increases the abundance of beneficial bacteria. However, 1500 mg kg -1  GML adversely affected the stability of the intestinal microbiota, significantly upregulating intestinal antimicrobial peptide-related genes and tumor necrosis factor-alpha levels (P < 0.05). In summary, 1000 mg kg -1  GML was proven to enhance the growth performance, lipid absorption and metabolism, humoral immune response, and gut microbiota condition of P. vannamei, with no negative physiological effects., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Microalgae are currently considered an attractive source of highly valuable metabolites potentially exploitable as anticancer agents, nutraceuticals and cosmeceuticals and for bioenergy purposes. Their ease of culturing and their high growth rates further promote their use as raw material for the production of specialty products. In the present paper, we focused our attention on specific glycerol-based lipid compounds, monoacylglycerols (MAGs), which displayed in our previous studies a selective cytotoxic activity against the haematological U-937 and the colon HCT-116 cancer cell lines. Here, we performed a quali/quantitative analysis of MAGs and total fatty acids (FAs) along with a profiling of the main lipid classes in a panel of 12 microalgal species, including diatoms and dinoflagellates. Our results highlight an inter- and intraspecific variability of MAG profile in the selected strains. Among them, Skeletonema marinoi (strain FE7) has emerged as the most promising source for possible biotechnological production of MAGs.

cis -12-oxo-Phytodieneoic acid-α-monoglyceride ( 1 ) was isolated from Arabidopsis thaliana . The chemical structure of 1 was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the cis -OPDA moiety in 1 was determined by comparison of 1 H NMR spectra and ECD measurements. With respect to the absolute configuration of the β-position of the glycerol backbone, the 2:3 ratio of ( S ) to ( R ) was determined by making ester-bonded derivatives with ( R )-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride and comparing 1 H NMR spectra. Wounding stress did not increase endogenous levels of 1 , and it was revealed 1 had an inhibitory effect of A. thaliana post germination growth. Notably, the endogenous amount of 1 was higher than the amounts of (+)-7- iso -jasmonic acid and (+)- cis -OPDA in intact plants. 1 also showed antimicrobial activity against Gram-positive bacteria, but jasmonic acid did not. It was also found that α-linolenic acid-α-monoglyceride was converted into 1 in the A. thaliana plant, which implied α-linolenic acid-α-monoglyceride was a biosynthetic intermediate of 1 .

The objective of this study was to evaluate the effects of different levels of glycerol monolaurate (GML) on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens. A total of 480 Hy-Line Variety Brown hens (age 54 wk) were randomly assigned to 5 treatments: the control group (basal diet) and 4 GML groups (basal diet supplemented with 100, 200, 300, and 400 mg/kg GML). Each treatment consisted of 8 replicates with 12 hens each and the trial lasted for 8 wk. The results showed that dietary inclusion of GML increased the ADFI in the entire experimental period and the average egg weight in wk 5 to 8 and wk 1 to 8 of the experiment (linear, P < 0.05). Dietary GML addition linearly increased albumen height, Haugh unit and yolk color, and quadratically increased eggshell thickness (P < 0.05). The serum SOD activity, T-AOC and IgG concentrations in the 200 mg/kg GML group, and GSH-Px activity in 200 and 300 mg/kg GML groups were increased, while the MDA concentration in 200 and 300 mg/kg GML groups was decreased than those in the control group (P < 0.05). The jejunal villus height and villus height: crypt depth in 300 mg/kg GML group were higher than that in the control group (P < 0.05). The mRNA expression of TLR4, IL-1β and TNF-α in spleen and jejunum decreased with the increase of dietary GML concentration (linear, P < 0.05). In conclusion, dietary GML supplementation could improve egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens, and dietary 300 mg/kg GML inclusion is suggested., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Supplementation of a combination of lysolecithin, a synthetic emulsifier, and monoglycerides (LEX) in liquid and dry form to broiler diets with different energy levels was investigated to determine their effect on performance, litter quality and subsequent occurrence of footpad lesions. One thousand two hundred and forty-eight-day-old Ross 308 broilers were assigned to 1 of 6 treatments for a 42-day study: a basal diet with a normal energy content (NE); NE + 300 g/t LEX in liquid form (LEL); NE + 500 g/t LEX in dry form (LED); a basal diet with low energy (LE, -90 kcal/kg starter, -100 kcal/kg grower, finisher), LE + 300 g/t LEL and a LE + 500 g/t LED. Each treatment consisted of 13 pens of 16 birds each. Diets were fed in 3 phases (starter d 0-10, grower d 11-21, finisher d 22-42). Feed intake and weight were measured on d 0, 10, 21, and 42. On d 42 a litter sample was collected from each pen and 2 birds per pen were assessed for footpad lesions and breast scald. Data were analyzed using JMP 16, with means separation achieved using Tukey's HSD; significance was assumed at P < 0.05. Results showed a higher (P < 0.05) cumulative bodyweight gain with LEX supplementation (NE CON = 2,718 g, NE+LED = 2,829, NE+LEL = 2,895, LE CON = 2,722, LE+LED = 2,787, LE+LEL = 2,893; P = 0.0027). An increased feed intake was observed for the LE diets, however cumulative FCR of LE+LED and LE+LEL remained equal to the NE control (1.657 NE CON, 1.657 LE+LED, 1.623 LE+LEL; P > 0.05), suggesting LEX enabled the birds to compensate for the energy gap. Litter dry matter was significantly improved with both LED and LEL supplementation compared to the control groups, and resulted in lower (P < 0.05) occurrence and severity of footpad lesions and breast scalds. Considering the income over feed cost (IOFC) of the NE treatment as the reference point for comparison, all other treatments improved profitability, with NE+LEL and LE+LEL achieving the greatest IOFC with 154.58 and 175.96 €/1,000 birds respectively. In conclusion, feeding broilers a combination of lysophospholipids, a synthetic emulsifier and monoglycerides resulted in improved bird performance. The use of the LEX also improved litter quality and footpad health, therefore improving animal welfare indicators such as breast scald and footpad measurements., Competing Interests: DISCLOSURES The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexandra Wealleans reports article publishing charges was provided by Kemin Europa NV. Kemin Europa NV funded the study, and provided support in the form of salary for A. W., A. D., D. G. S., and R. S. No other conflicts of interest are declared., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We report electrochemical impedance spectroscopy measurements to characterize the membrane-disruptive properties of medium-chain fatty acid and monoglyceride mitigants interacting with tethered bilayer lipid membrane (tBLM) platforms composed of E. coli bacterial lipid extracts. The tested mitigants included capric acid (CA) and monocaprin (MC) with 10-carbon long hydrocarbon chains, and lauric acid (LA) and glycerol monolaurate (GML) with 12-carbon long hydrocarbon chains. All four mitigants disrupted E. coli tBLM platforms above their respective critical micelle concentration (CMC) values; however, there were marked differences in the extent of membrane disruption. In general, CA and MC caused larger changes in ionic permeability and structural damage, whereas the membrane-disruptive effects of LA and GML were appreciably smaller. Importantly, the distinct magnitudes of permeability changes agreed well with the known antibacterial activity levels of the different mitigants against E. coli , whereby CA and MC are inhibitory and LA and GML are non-inhibitory. Mechanistic insights obtained from the EIS data help to rationalize why CA and MC are more effective than LA and GML at disrupting E. coli membranes, and these measurement capabilities support the potential of utilizing bacterial lipid-derived tethered lipid bilayers for predictive assessment of antibacterial drug candidates and mitigants.

Glycerol monolaurate (GML) is a food safe emulsifier and a kind of MCFA monoglyceride that has been proven to confer positive benefits in improving animal health, production and feed digestibility as a feed additive. This study aims to evaluate whether supplementation of a sow diet with GML could affect the intestinal barrier function and antioxidant status of newborn piglets and to explore its regulatory mechanism. A total of 80 multiparous sows were divided into two groups, which were fed a basal diet or a basal diet supplemented with 0.1% GML. The results indicated that maternal supplementation with GML significantly increased fat, lactose and protein in sow colostrum, as well as fat and protein in sow 14-day milk ( P < 0.05). The results showed that GML significantly reduced the concentrations of IL-12 in the duodenum, TNF-α, IL-1β and IL-12 in the jejunum, and IL-1β in the ileum of piglets ( P < 0.05). Higher concentrations of T-AOC, T-SOD, GSH and GSH-Px and lower MDA in the intestine were observed in the GML group than in the control group. Correspondingly, the villi height, crypt depth and the ratio of villi height to crypt depth (V/C) in the jejunum and the V/C in the ileum in the GML group were significantly higher than those in the control group ( P < 0.05). Moreover, the GML group displayed significantly increased protein abundance of zonula occludens (ZO)-1, occludin, and claudin-1 in the small intestine ( P < 0.05), mRNA expression of mucins (MUCs) in the small intestine ( MUC-1 , MUC-3 and MUC-4 ), and mRNA expression of porcine beta defensins (pBDs) in the duodenum ( pBD1 and pBD2 ), jejunum ( pBD1 , pBD2 and pBD129 ) ( P < 0.05), and ileum ( pBD2 , pBD3 and pBD114 ) ( P < 0.05). Further research showed that GML significantly reduced the phosphorylation of the NF-κB/MAPK pathways in the small intestine ( P < 0.05). In addition, the results of 16S rDNA sequencing showed that maternal supplementation with GML altered the colonic microbiotic structure of piglets, and reduced the relative abundance of Escherichia shigella . In summary, a sow diet supplemented with GML enhanced the offspring's intestinal oxidative stability and barrier function and attenuated the offspring's intestinal inflammatory response, possibly by suppressing the activation of the NF-κB/MAPK pathways.

The present study was undertaken to evaluate the efficacy of 2 graded levels (0.03 and 0.05% of diet) of a monoglyceride blend containing butyric, caprylic, and capric acids in broilers' diet for optimizing gut structure and animal growth performance. For this purpose, a total of 210, one-day-old male Ross 308 broiler chicks were randomly allocated to 3 experimental treatments using 7 replicates each and 10 birds/replicate. The treatment groups involved supplementation of blend of short and medium chain fatty acids at the level of 0, 0.03, and 0.05% of the diet for 42 d. The incorporation of mixes of monoglycerides into broilers' diet linearly improved BWG between d 0 and 21 (P = 0.034). At the end of trial, however, no significant changes were observed in performance indexes (BWG, FI, FCR). Jejunal morphometric parameters (villus height, crypt depth, and their ratio) remained unaltered with the monoglyceride supplementation on d 21. The results further showed that monoglycerides supplementation increased the goblet cell counts along the jejunal villi (P = 0.034) and crypt regions (P = 0.022), as well as it effectively modulated the mRNA abundances of tight junction protein (ZO-1, P = 0.033) and nutrient transporters (SGLT, PePT1; P = 0.005, 0.023, respectively) in the jejunum. Moreover, the downregulation in mRNA abundance of TNFα (P = 0.030) was observed with the monoglyceride supplementation. The SCFAs analysis of cecal contents showed no notable differences with monoglyceride blend supplementation when compared to the unsupplemented group. Collectively, high goblet cell numbers in the jejunum along with downregulation of the mRNA abundances of pro-inflammatory cytokines, upregulation of tight junction proteins, and nutrient transporters showed favorable responses of low doses of monoglycerides blend in broiler feeding. Further studies should be conducted in different rearing conditions to examine the effectiveness of such low levels of a monoglyceride blend in the modulation of gut structure, its functionality and animal performance., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The effect of acylglycerols on the thermal inactivation of lactic acid bacteria used in the production of fermented products was studied. The starting point was the observation of an increase in thermal sensitivity in the presence of an emulsifier based on mono- and diacylglycerols in the culture medium. Analysis of the emulsifier showed that monoacylglycerols were the compounds responsible for this effect, with monopalmitin being the main contributor. Monostearin, on the other hand, showed significantly less potentiating effect. Interestingly, monoacylglycerols showed a greater bactericidal effect when used individually than when used in combination. On the other hand, the rate of thermal inactivation observed in reconstituted skim milk emulsions was lower than in peptone water emulsions, showing that the presence of proteins and colloidal particles increased the resistance of bacteria to heat treatment. With respect to pH values, a reduction in pH from 6.6 to 5.5 promoted an increase in the rate of thermal death. However, at pH = 5.5, the enhancing bactericidal effect was only detectable when the heat treatment was performed at low temperatures but not at high temperatures. This finding is of interest, since it will allow the design of moderate heat treatments, combining the use of temperature with the addition of acylglycerols, to prolong the shelf life of products fermented with lactic acid bacteria, and minimizing the destruction of desirable compounds that were obtained by the fermentation process., (© 2022. The Author(s).)

Porcine reproductive and respiratory syndrome (PRRS) is a disease with a major economic impact in the global pig industry, and this study aims to identify potential anti-PRRSV drugs. We examined the cytotoxicity of four medium-chain fatty acids (MCFAs) (caprylic, caprylic monoglyceride, decanoic monoglyceride, and monolaurin) and their inhibition rate against PRRSV. Then the MCFAs with the best anti-PRRSV effect in in vitro assays were selected for subsequent in vivo experiments. Potential anti-PRRSV drugs were evaluated by viral load assay, pathological assay, and cytokine level determination. The results showed that caprylic monoglyceride (CMG) was the least toxic to cells of the four MCFAs, while it had the highest PRRSV inhibition rate. Then the animals were divided into a low-CMG group, a medium-CMG group, and a high-CMG group to conduct the in vivo evaluation. The results indicated that piglets treated with higher concentrations of caprylic monoglyceride were associated with lower mortality and lower viral load after PRRSV infection (p < 0.05). The pulmonary pathology of the piglets also improved after CMG treatment. The levels of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, TNF-α) were significantly downregulated, and the levels of anti-inflammatory cytokine (IL-10) were significantly upregulated in the CMG-treated piglets compared to the positive control group (p < 0.05). Taken together, the present study revealed for the first time that caprylic monoglyceride has strong antiviral activity against PRRSV in vitro and in vivo, suggesting that caprylic monoglyceride could potentially be used as a drug to treat PRRS infection.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. β-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL -1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL -1 for E. coli , and 750-950 µg mL -1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

Glycerol monodecanoate (GMD) is a medium-chain monoacylglycerol that possesses emulsifying and antibacterial properties. The common emulsifiers carboxymethylcellulose and polysorbate-80 have been reported to cause intestinal microbiota dysbiosis and metabolic disturbances. Glycerol monolaurate (GML), another medium-chain monoacylglycerol, is often used as an emulsifier and could improve metabolism by regulating the gut microbiota. However, research on the effects of GMD on the metabolism and gut microbiota remains scarce. Mice were fed a normal chow diet with or without GMD (150, 800, and 1600 mg kg -1 ) for 22 weeks. Metabolism indicators and related genes, gut microbiota, and fecal SCFAs were analyzed. The results demonstrated that GMD significantly improved insulin sensitivity, reduced the serum LPS level, and decreased pro-inflammation cytokines including IL-1β, tumor necrosis factor (TNF), and monocyte chemotactic protein 1 (MCP-1). Additionally, 150 and 1600 mg kg -1 GMD could significantly lower the blood glucose content. 1600 mg kg -1 GMD improved cholesterol metabolism and related gene expression compared to 150 and 800 mg kg -1 GMD. Moreover, 150 and 800 mg kg -1 GMD up-regulated the abundance of Lactobacillus and Turicibacter , while 1600 mg kg -1 GMD significantly up-regulated the abundance of Bifidobacterium . Our findings indicated that different doses of GMD had inconsistent effects on lipid metabolism by differentially altering the gut microbiota composition. Meanwhile, all doses of GMD showed excellent effects on increasing insulin sensitivity and improving inflammation.

Glycerol monolaurate (GML) is a naturally occurring antimicrobial agent used commercially in numerous products and food items. GML is also used as a homeopathic agent and is being clinically tested to treat several human diseases. In addition to its anti-microbial function, GML suppresses immune cell proliferation and inhibits primary human T cell activation. GML suppresses T cell activation by altering membrane dynamics and disrupting the formation of protein clusters necessary for intracellular signaling. The ability of GML to disrupt cellular membranes suggests it may alter other cell types. To explore this possibility, we tested how GML affects human B cells. We found that GML inhibits BCR-induced cytokine production, phosphorylation of signaling proteins, and protein clustering, while also changing cellular membrane dynamics and dysregulating cytoskeleton rearrangement. Although similar, there are also differences between how B cells and T cells respond to GML. These differences suggest that unique intrinsic features of a cell may result in differential responses to GML treatment. Overall, this study expands our understanding of how GML impacts the adaptive immune response and contributes to a broader knowledge of immune modulating monoglycerides., (© 2022. The Author(s).)

Monoacylglycerol lipase (MAGL) is the enzyme responsible for the metabolism of 2-arachidonoylglycerol in the brain and the hydrolysis of peripheral monoacylglycerols. Many studies demonstrated beneficial effects deriving from MAGL inhibition for neurodegenerative diseases, inflammatory pathologies, and cancer. MAGL expression is increased in invasive tumors, furnishing free fatty acids as pro-tumorigenic signals and for tumor cell growth. Here, a new class of benzylpiperidine-based MAGL inhibitors was synthesized, leading to the identification of 13 , which showed potent reversible and selective MAGL inhibition. Associated with MAGL overexpression and the prognostic role in pancreatic cancer, derivative 13 showed antiproliferative activity and apoptosis induction, as well as the ability to reduce cell migration in primary pancreatic cancer cultures, and displayed a synergistic interaction with the chemotherapeutic drug gemcitabine. These results suggest that the class of benzylpiperidine-based MAGL inhibitors have potential as a new class of therapeutic agents and MAGL could play a role in pancreatic cancer.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yi, Ji, Wu, Wang, Guo, Wang, Zhao and Hou.)

Outbreaks of African swine fever virus (ASFv) and porcine epidemic diarrhoea virus (PEDv) have revealed the susceptibility of livestock to disease transmitted through feed. Several viruses, including PEDv, survive in feed and may introduce disease that causes significant morbidity and mortality. In 2013, PEDv, which causes severe diarrhoea and vomiting, reached North America after spreading for decades across Eurasia. The global exchange of ingredients has created demand for products that prevent disease transmission from feed. Formaldehyde-based products are highly effective at inactivating enveloped viruses when applied at 3.25 kg/t. Alternative products to formaldehyde, including carboxylic acids, essential oils and medium chain fatty acids (MCFAs), have exhibited mixed efficacy against PEDv and require application rates higher than formaldehyde. Amphiphilic molecules like MCFAs disrupt the bilayer-lipid membranes that protect viral nucleic acids through the formation of micelles. Monoglycerides form micelles at lower concentrations than MCFAs, which suggests they may be more potent against enveloped viruses. The potential efficacy of monoglycerides against enveloped viruses in feed led to the development and examination of an experimental monoglyceride blend. The proprietary monoglyceride blend significantly (p < .0001) reduced PEDv viability in vitro after application to feed at 1.5, 2.5 and 3.5 kg/t. The monoglyceride was tested in a natural feeding behaviour challenge model in piglets. The feed was contaminated with ice-blocks containing viable PEDv, and the piglets were exposed to PEDv through the feed bin for 20 days. At the end of the 20-day challenge period, all pigs were rectally swabbed and tested for PEDv by qPCR. In the untreated control group 54.8% of the piglets tested positive for PEDv, whereas none of the MCFA-treated feed (10 kg/t inclusion) transmitted PEDv. Strikingly, the monoglyceride-treated groups (1.5, 2.5 and 3.5 kg/t) all exhibited 100% protection from PEDv. These data support the use of this proprietary monoglyceride blend in mitigation and prevention of viral disease transmission to piglets from contaminated feed., (© 2021 Kemin Industries, Inc. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

Zein is renewable plant protein with valuable film-forming properties that can be used as a packaging material. It is known that the addition of natural cross-linkers can enhance a film's tensile properties. In this study, we aimed to prepare antimicrobial zein-based films enriched with monolaurin, eugenol, oregano, and thyme essential oil. Films were prepared using the solvent casting technique from ethanol solution. Their physicochemical properties were investigated using structural, morphological, and thermal techniques. Polar and dispersive components were analyzed using two models to evaluate the effects on the surface free energy values. The antimicrobial activity was proven using a disk diffusion method and the suppression of bacterial growth was confirmed via a growth kinetics study with the Gompertz function. The films' morphological characteristics led to systems with uniform distribution of essential oils or eugenol droplets combined with a flat-plated structure of monolaurin. A unique combination of polyphenolic eugenol and amphiphilic monoglyceride provided highly stretchable films with enhanced barrier properties and efficiency against Gram-positive and Gram-negative bacteria, yeasts, and molds. The prepared zein-based films with tunable surface properties represent an alternative to non-renewable resources with a potential application as active packaging materials.

Helicobacter pylori infection is the most common cause of gastritis and gastric ulcers. Considering the severe side effects of current antibiotic therapies, it is crucial to find an alternate treatment for H. pylori infection. In this study, we investigated the anti- H. pylori effects of a newly isolated strain of Lactobacillus plantarum (pH3A), monolaurin, grapefruit seed extract (GSE), and their synergies in vitro and in vivo . Monolaurin and GSE suppressed H. pylori growth and urease activity at a minimal inhibitory concentration (MIC) of 62.5 ppm. Live cells and cell-free culture supernatant (CFCS) of L. plantarum pH3A with or without pH adjustment also significantly inhibited H. pylori growth. Although synergy was not observed between monolaurin and GSE, the addition of CFCS significantly enhanced their anti- H. pylori activities. Moreover, L. plantarum pH3A significantly decreased the ability of H. pylori to adhere to AGS cells and interleukin (IL)-8 production in the H. pylori -stimulated AGS cell line. The addition of GSE or monolaurin strengthened these effects. In the in vivo study, H. pylori colonization of the mouse stomach and total serum IgG production were significantly reduced by L. plantarum pH3A treatment, but the addition of monolaurin or GSE did not contribute to these anti- H. pylori activities. Therefore, the L. plantarum pH3A strain can potentially be applied as an alternative anti- H. pylori therapy, but evidence of its synergy with monolaurin or GSE in vivo is still lacking.

Epidemiologic and preclinical studieshave shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride (MAG-DHA), a docosahexaenoic acid sn-1-monoacylglycerol does not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol, or DHA-ethyl ester. However, the anticancer actions and underlying mechanisms of MAG-DHA on breast cancer remain to be assessed. In this study, MAG-DHA induced significant growth inhibition in MCF-7 and MDA-MB-231 breast cancer cells in a dose-dependent manner. MAG-DHA treatment (80 µM) led to 83.8 and 94.3% growth inhibition between MCF-7 and MDA-MB-231 cells, respectively. MAG-DHA-induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase-3, poly (ADP-ribose) polymerase (PARP) and caspase-12. In particular, MAG-DHA-induced apoptosis was triggered by oxidative stress-mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK-eIF2α pathway in ER. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG-DHA group (0.271 cm 3 ) and control group (0.875 cm 3 ) after 15 daily MAG-DHA treatments. The in vitro antibreast cancer mechanism of MAG-DHA was supported by the in vivo xenograft model. In addition, MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Our data suggested that MAG-DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer., (© 2021 Institute of Food Technologists®.)

Background: This experiment tested the impact of the combined supplementation of glycerol monolaurate (GLM) and oregano essential oil (EO) to broiler diets. Growth performance, metabolic response, immune status, apparent ileal digestibility coefficient (AID%), and intestinal histomorphology were assessed. Three-day-old Ross-308 broilers (76.62 g ± 0.50, n = 240) were randomly allocated into 4 experimental groups (6 replicates/group and 10 chicks/replicate). Birds were fed corn-soybean meal basal diets supplemented with four levels of GLM and oregano EO blend: 0, 0.15, 0.45, and 0.75% for 35 days., Results: During the starter period, dietary GLM and oregano EO did not show significant (P > 0.05) changes in growth performance. During the grower period, GLM and oregano EO supplemented groups showed a linear and quadratic decline in FCR. During the finisher and overall performance, a linear increase in the body weight (BW), body weight gain (BWG), the protein efficiency ratio (PER), and relative growth rate (RGR), and a linear decrease in the FCR at 0.75% dietary level of GLM and oregano EO compared to the control. The broken-line regression model showed that the optimum dietary level of GLM and oregano EO blend was 0.58% based on final BW and FCR. The 0.45% or 0.15% dietary level of supplemented additives lowered (P < 0.05) the AID% of threonine and arginine, respectively, with no change in the AID% of other assessed amino acids at all dietary levels. Muscle thickness in jejunum and ileum in all dietary supplemented groups was increased (P < 0.05); however, such increase (P < 0.05) in the duodenum was shown at 0.45 and 0.75% dietary levels. All GLM and oregano EO supplemented groups showed increased (P < 0.05) duodenal, jejunal, and ileal villus height. The 0.15 and/or 0.75% dietary levels of supplemented additives increased (P < 0.05) the ileal and duodenal crypt depth, respectively, with a decreased (P < 0.05) duodenal crypt depth at 0.15% dietary level. The goblet cell count in ileum decreased (P < 0.05) in all GLM and oregano EO supplemented groups, but this decreased count (P < 0.05) was detected in jejunum at 0.45 and 0.75% dietary levels. The GLM and oregano EO supplemented groups did not show significant (P > 0.05) changes in the assessed metabolic and immune status parameters. Economically, the total return and performance index was increased at 0.75% dietary level., Conclusion: Better growth performance was achieved at a 0.75 % dietary level of GLM and oregano EO by improving most intestinal morphometric measures. The optimum dietary level detected was 0.58%. The lack of influence of supplemented additives on chickens' immune and metabolic responses could indicate a lack of synergy between GLM and oregano EO., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kong, Wang, Xiao, Zhu and Song.)

The efficiency of filtration membranes is substantially lowered by bacterial attachments and potential fouling processes, which reduce their durability and lifecycle. The antibacterial and antifouling properties exhibited by the added materials play a substantial role in their application. We tested a material poly(vinylidene fluoride)- co -hexafluoropropylene (PDVF- co -HFP) based on an electrospun copolymer, where an agent was incorporated with a small amount of ester of glycerol consecutively with caprylic, capric, and lauric acids. Each of these three materials differing in the esters (1-monoacylglycerol, 1-MAG) used was prepared with three weighted concentrations of 1-MAG (1, 2, and 3 wt %). The presence of 1-MAG with an amphiphilic structure resulted in the hydrophilic character of the prepared materials that contributed to the filtration performance. The tested materials (membranes) were characterized with rheological, optical (scanning electron microscopy, SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and other methods to evaluate antibacterial and antifouling activities. The pure water flux was 6 times higher than that of the neat PVDF- co -HFP membrane when the added 1-MAG attained only 1 wt %. It was experimentally shown that the PVDF- co -HFP/1-MAG membrane with high wettability improved antibacterial activity and antifouling ability. This membrane is highly promising for water treatment due to the safety of antibacterial 1-MAG additives.

Glycerol monolaurate (GML) is a monoglycerol ester of the fatty lauric acids, which has a wide-spectrum antimicrobial capacity, but fails to inactivate Gram-negative bacteria, especial Salmonella. To enhance the population reduction rate of GML for Salmonella, this reagent was combined with three disinfectants: lactic acid (LA), cetylpyridinium chloride (CPC), and trisodium phosphate (TSP), which can present acid, neutral, and alkaline in solution, respectively. The results showed that the 1% GML and a complex disinfectant (0.5% GML-0.025% LA) could powerfully inactivate Salmonella. Their population reduction rates respectively were able to achieve 99.92% and 98.29% with the vortex treatment, indicating that the vortex treatment could improve GML to destruct the outer membrane of Salmonella. During the simulation test of the soaking and rinse processing of chicken, for a short time (0 h), the effect of 0.5% GML-0.025% LA compound was better and more suitable for instantaneous inactivation than others, while for a long time (4 h), 1% GML exhibited a better bactericidal effect, which indicated it to be more suitable for long-term bacteriostasis. The characterization of color and texture for chicken samples were determined using Colormeter Ci7600, TA.XT Plus and Hyper-spectral Imager, which demonstrated that all samples treated by these complex disinfectants were not significantly different from untreated group. In conclusion, GML is a potential and superior disinfectant for the chicken process., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12-14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.

Glycerol monolaurate (GML), a member of medium-chain α-monoglycerides (MG), is proved to be beneficial for productive performance, feed efficiency, and health of broilers based on recent research. The present study aims to evaluate the effect of MG mixture rich in GML and glycerol monodecanoate on performance, intestinal development, serum parameters, carcass yield, and muscle composition in broilers. A total of 528 chicks were weighed and randomly assigned into 4 groups (22 chicks/replicate, 6 replicates/group) for a 56-d experiment. The control group received a basal diet containing 0 mg/kg MG (CON), and the treated groups fed basal diets containing 300 (MG300), 450 and 600 mg/kg MG. The results revealed that the BW (P < 0.05), ADG, and ADFI were notably increased in MG-containing groups during the finisher phase compared with the CON group. Remarkable intestinal improvements were observed in the duodenum and jejunum of MG-treated groups, but no statistical differences were obtained. Dietary MG significantly (P < 0.05) increased the serum high-density lipoprotein cholesterol, total protein, and superoxide dismutase content in broilers. Inclusion of 300 mg/kg MG in diet increased the eviscerated yield (P = 0.066), leg muscle (P < 0.01) and breast muscle yield (P = 0.083), and improved the fresh meat quality with reduced drip loss (P < 0.01) and pH decline (P < 0.01) compared with the CON group. Moreover, the saturated fatty acid (P = 0.073), flavor amino acid (P < 0.05), and total amino acid (P < 0.05) content was notably higher in the muscle of the MG300 group than that in the CON group. In summary, these findings revealed that mixed MG can be used as an effective and novel feed supplement to improve productive performance and quality of broilers., (Copyright © 2020. Published by Elsevier Inc.)

The present study aimed to evaluate the effects of medium-chain α-monoglycerides (MG) on productive performance, egg quality, serum biochemical indices, and gut microbiota in laying hens. A total of 252 40-wk-old Hy-Line Brown laying hens were randomly allotted into two groups (21 hens per replicate, 6 replicates per group) and fed with a basal diet (CON group) or a basal diet containing 300 mg/kg of MG (MG300 group). The eggs laid were recorded daily on a replicate basis, and egg quality was measured at 48, 56, and 64 wk of age. At the end of this trial, three randomly selected hens from each replicate were slaughtered, and the serum and cecal digesta were collected for analysis of serum biochemical indices and sex hormones and gut microbiota composition determination. The results revealed that the laying rate was significantly (P < 0.05) increased in the MG300 group, and the feed conversion ratio was decreased (P < 0.01) during 40-64 wk of age. The eggshell strength at 56 wk of age and eggshell thickness at 56 and 64 wk of age were significantly (P < 0.05) increased in the MG300 group. In addition, dietary MG significantly (P < 0.05) increased levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, glucose, Ca, serum total cholesterol, triglycerides, and high-density lipoprotein cholesterol, but decreased the lipopolysaccharide level. Notably, MG supplementation increased (P < 0.05) the relative abundance of genera Lachnospiraceae&#95;NK4A136&#95;group, Romboutsia, Syntrophomonas, Victivallis, Ruminiclostridium&#95;6, and Family&#95;XIII&#95;UCG&#95;001 (P < 0.01) and simultaneously decreased the abundances of Proteobacteria, Faecalibacterium, Alistipes, Cerasicoccus, Schlegelella, and Treponema&#95;2. Spearman's correlation analysis indicated that the differentiated genera were significantly associated with the serum biochemical indices and sex hormone. In summary, the present study revealed that dietary supplementation with MG can improve productive performance and egg quality by modulating gut microbiota, suggested that MG may act as an efficient feed supplement in aged hens., (Copyright © 2020. Published by Elsevier Inc.)

The objective of this study was to evaluate the chemical composition and fatty acid profile of broilers fed diets containing glycerol monolaurate (GML) in place of antimicrobials. Groups: T0 group used as control; T100, T200, and T300 groups received diets supplemented with 100, 200, and 300 mg/kg of GML, respectively. The feed mixture used in the poultry feed during the four phases of the production cycle (days 1 to 7; 8 to 21; 22 to 35; and 36 to 42 of birds age) showed similar levels of protein, lipid and ash, as well as fatty acid profiles. Samples of frozen breasts from chickens slaughtered at 42 days of age were used for chemical gross composition and fatty acid analysis. We observed lower lipid levels in the meat of broilers in the T200 and T300 groups than in the T0 group. Lower lipid peroxidation occurred in the meat of animals that consumed GML in respect to control. Total saturated fatty acid percentage was lower, while total polyunsaturated fatty acid percentage was higher in the meat of broilers fed GML than in the control group. We conclude that the increase in GML concentrations alters the lipid profile of broiler meat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions., Results: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong M Pro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent M Pro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant M Pro inhibition.

Staphylococcus aureus is a highly significant infection problem in health care centers, particularly after surgery. It has been shown that nearly 80% of S. aureus infections following surgery are the same as those in the anterior nares of patients, suggesting that the anterior nares is the source of the infection strain. This has led to the use of mupirocin ointment being applied nasally to reduce infections; mupirocin resistance is being observed. This study was undertaken to determine whether gel composed of 5% glycerol monolaurate solubilized in a glycol-based, nonaqueous gel (5% GML gel) could be used as an alternative. In our study, 40 healthy human volunteers swabbed their anterior nares for 3 days with the 5% GML gel. Prior to swabbing and 8 to 12 h after swabbing, S. aureus and coagulase-negative staphylococcal CFU per milliliter were determined by plating the swabs on mannitol salt agar. Fourteen of the volunteers had S. aureus in their nares prior to 5% GML gel treatment, most persons with the organisms present in both nares; five had pure cultures of S. aureus All participants without pure culture of S. aureus were cocolonized with S. aureus and coagulase-negative staphylococci. Five of the S. aureus strains produced the superantigens commonly associated with toxic shock syndrome, though none of the participants became ill. For both S. aureus and coagulase-negative staphylococci, the 5% GML gel treatment resulted in a 3-log-unit reduction in microorganisms. For S. aureus , the reduction persisted for 2 or 3 days. IMPORTANCE In this microflora study, we show that a 5% glycerol monolaurate nonaqueous gel is safe for use in the anterior nares. The gel was effective in reducing Staphylococcus aureus nasally, a highly significant hospital-associated pathogen. The gel may be a useful alternative or additive to mupirocin ointment for nasal use prior to surgery, noting that 80% of hospital-associated S. aureus infections are due to the same organism found in the nose. This gel also kills all enveloped viruses tested and should be considered for studies to reduce infection and transmission of coronaviruses and influenza viruses., (Copyright © 2020 Schlievert and Peterson.)

Inactivation of Bacillales and Clostridiales spores is of interest, since some cause food spoilage and human diseases. A recent publication (mSphere 3: e00597-1, 2018) reported that glycerol monolaurate (GML) in a non-aqueous gel (GMLg) effectively killed spores of Bacillus subtilis, Bacillus cereus and Clostridioides difficile, and Bacillus anthracis spores to a lesser extent. We now show that (i) the B. subtilis spores prepared as in the prior work were impure; (ii) if spore viability was measured by diluting spores 1/10 in GMLg, serially diluting incubations 10-fold and spotting aliquots on recovery plates, there was no colony formation from the 1/10 to 1/1000 dilutions due to GMLg carryover, although thorough ethanol washes of incubated spores eliminated this problem and (iii) GMLg did not kill highly purified spores of B. subtilis, B. cereus, Bacillus megaterium and C. difficile in 3-20 h in the conditions used in the recent publication. GMLg also gave no killing of crude B. subtilis spores prepared as in the recent publication in 5 h but gave ~1·5 log killing at 24 h. Thus, GMLg does not appear to be an effective sporicide, although the gel likely inhibits spore germination and could kill spores somewhat upon long incubations. SIGNIFICANCE AND IMPACT OF THE STUDY: Given potential deleterious effects of spores of Bacillales and Clostridiales, there is an ongoing interest in new ways of spore killing. A recent paper (mSphere 3: e00597-1, 2018) reported that glycerol monolaurate (GML) in a non-aqueous gel (GMLg) effectively killed spores of many species. We now find that (i) the Bacillus subtilis spores prepared as in the previous report were impure and (ii) GMLg gave no killing of purified spores of Bacillales and Clostridiales species in ≤5 h under the published conditions. Thus, GMLg is not an effective sporicide, though may prevent spore germination or kill germinated spores., (© 2020 The Society for Applied Microbiology.)

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., (Copyright © 2020 Welch et al.)

This study determined the potential of formic acid plus monolaurin (FA + ML) as an alternative to antibiotics in diet when piglets are challenged with ETEC. Piglets fed the FA + ML diet had lower fecal score and rectal temperature after the ETEC challenge. In addition, FA + ML supplementation induced lower plasma TNF-α, IL-6, and IL-1β concentration postchallenge, downregulated the mRNA expression of TNF-α, IL-1β, IL-6, and TLR4 in the ileum and TLR4 and CFTR in the jejunum. Phosphorylation levels of NF-κB p65 and MAPK p38 were reduced in the ileum of piglets fed FA + ML diet. Supplementation of FA + ML increased the relative abundance of genera Lactobacillus especially Lactobacillus amylovorus species and decreased the genus abundances of Actinobacillus , unidentified Enterobacteriaceae , Moraxella . Collectively, the combination of formic acid and monolaurin in diets have the potential to be an antibiotic alternative to mitigate inflammatory response in piglets challenged with ETEC.

In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate ( Lim -SLNs), stabilized with Poloxamer ® 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim -SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim -SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.

Herein, we report on the synthesis of a series of enantiomerically pure linear, iso-branched, and α-branched monoacyl glycerides (MAGs) in 63-72% overall yield. The ability of the MAGs to signal through human macrophage inducible C-type lectin (hMincle) using NFAT-GFP reporter cells was explored, as was the ability of the compounds to activate human monocytes. From these studies, MAGs with an acyl chain length ≥C22 were required for Mincle activation and the production of interleukin-8 (IL-8) by human monocytes. Moreover, the iso-branched MAGs led to a more pronounced immune response compared to linear MAGs, while an α-branched MAG containing a C-32 acyl chain activated cells to a higher degree than trehalose dibehenate (TDB), the prototypical Mincle agonist. Across the compound classes, the activity of the sn-1 substituted isomers was greater than the sn-3 counterparts. None of the representative compounds were cytotoxic, thus mitigating cytotoxicity as a potential mediator of cellular activity. Taken together, 6h (sn-1, iC26+1), 8a (sn-1, C32) and 8b (sn-3, C32) exhibited the best immunostimulatory properties and thus, have potential as vaccine adjuvants.

Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-chain PUFA. These were docosahexaenoic acid (DHA, 22:6 n 3) and arachidonic acid (ARA, 20:4 n 6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. Sequential window acquisition of all theoretical mass spectra (SWATH) - mass spectrometry massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. Results clearly demonstrated the ability of both ARA- and DHA-MAG to induce cell death in colon cancer cells, which suggests a direct relationship between chemical structure and antitumoral actions., Competing Interests: The authors declare no conflict of interest.

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, monovalerin, 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 monovalerin, 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.

Human milk has antimicrobial compounds and immunomodulatory activities. We investigated glycerol monolaurate (GML) in human milk versus bovine milk and infant formula for antimicrobial and anti-inflammatory activities. Human milk contained approximately 3000 µg/ml of GML, compared to 150 μg/ml in bovine milk and none in infant formula. For bacteria tested (Staphylococcus aureus, Bacillus subtilis, Clostridium perfringens, Escherichia coli), except Enterococcus faecalis, human milk was more antimicrobial than bovine milk and formula. The Enterococcus faecalis strain, which was not inhibited, produced reutericyclin, which is an analogue of GML and functions as a growth stimulant in bacteria that produce it. Removal of GML and other lipophilic molecules from human milk by ethanol extraction resulted in a loss of antibacterial activity, which was restored by re-addition of GML. GML addition caused bovine milk to become antimicrobial. Human milk but not bovine milk or formula inhibited superantigen and bacterial-induced IL-8 production by model human epithelial cells. GML may contribute beneficially to human milk compared to bovine milk or infant formula.

Scope: The gut microbiota plays an important role in the development of diet-induced obesity and metabolic syndrome. Glycerol monolaurate (GML), a widely consumed food emulsifier, is reported to promote metabolic disorder and gut microbiota dysbiosis in low-dose supplementation upon low-fat-diet feeding. However, little is known about whether GML produce the same effects in mice fed a high-fat diet (HFD)., Methods and Results: C57BL/6 mice are fed a HFD with or without GML supplementation (150, 300, and 450 mg kg -1 ) for 10 weeks. The results demonstrated that higher GML treatment (450 mg kg -1 ) ameliorates HFD-induced metabolic disorders, supported by prevented visceral fat deposition, improved hyperlipidemia, modulated hepatic lipid metabolism, and reduced serum proinflammatory cytokine, TNF-α. Additionally, all doses of GML attenuated circulating lipopolysaccharide load and insulin resistance. Notably, GML ameliorates HFD-induced gut microbiota dysbiosis, with increases in Bacteroides uniformis, Akkermansia, Bifidobacterium, and Lactobacillus and decreases in Escherichia coli, Lactococcus, and Flexispira. Spearman's correlation analysis indicates that these enriched specific genera are significantly associated with the metabolic improvements of GML., Conclusion: The findings identify the links between gut microbiota and GML-induced metabolic improvements, suggesting that the attenuation of HFD-induced metabolic disorders by higher GML supplementation may occur through targeting gut microbiota., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg -1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg -1 ) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg -1 GML improved the richness of Barnesiella , whereas a high dosage of GML (1600 mg kg -1 ) significantly increased the relative abundances of Clostridium XIVa , Oscillibacter and Parasutterella . The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

This review focuses on recent findings of the physiological and pharmacological role of non-endocannabinoid N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs) in the intestine and their involvement in the gut-brain signalling. Dietary fat suppresses food intake, and much research concerns the known gut peptides, for example, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK). NAEs and 2-MAGs represent another class of local gut signals most probably involved in the regulation of food intake. We discuss the putative biosynthetic pathways and targets of NAEs in the intestine as well as their anorectic role and changes in intestinal levels depending on the dietary status. NAEs can activate the transcription factor PPARα, but studies to evaluate the role of endogenous NAEs are generally lacking. Finally, we review the role of diet-derived 2-MAGs in the secretion of anorectic gut peptides via activation of GPR119. Both PPARα and GPR119 have potential as pharmacological targets for the treatment of obesity and the former for treatment of intestinal inflammation. LINKED ARTICLES: This article is part of a themed section on 8 th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc., (© 2018 The British Pharmacological Society.)

Pseudomonas aeruginosa is a ubiquitous microorganism that commonly causes hospital-acquired infections, including pneumonia, bloodstream and urinary tract infections and it is well known for chronically colonising the respiratory tract of patients with cystic fibrosis, causing severe intermittent exacerbation of the condition. P. aeruginosa may appear in the free form cell but also grows in biofilm communities adhered to a surface. An alternative to conventional antimicrobial agents are nanoparticles that can act as carriers for antibiotics and other drugs. In this context, the study aimed to characterise and verify the anti-biofilm potential of GML Nanocapsules against P. aeruginosa. The nanocapsules showed a mean diameter of 190.7 nm, polydispersion index of 0.069, the zeta potential of -23.3 mV. The microdilution test showed a MIC of 62.5 μg/mL to GML and 15.62 μg/mL to GML Nanocapsules. The anti-biofilm experiments demonstrated the significant reduction of biomass, proteins, polysaccharide and viable P. aeruginosa in biofilm treated with GML Nanocapsules while the free GML did not cause an effect. The AFM images showed a decrease in a biofilm which received GML. The positive results suggest an alternative for the public health trouble related to infections associated with biofilm., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The cytotoxicity of monomyristin (MM), a monoacylglycerol, was investigated against cervical cancer cells (HeLa) and two normal cells (Vero and endometrial epithelial cells). MM exhibited cytotoxicity specifically to HeLa cells and not against normal cells except at the highest investigated doses (> 500 μg/mL). MM was showed to increase apoptotic dead cells by intrinsic mitochondrial pathway. To overcome the poor water solubility of MM and increase its efficacy against HeLa cells, MM was encapsulated into dextran-covered polylactide (PLA) nanoparticles (NPs). NPs comprised a PLA core which encapsulated MM and a superficial layer of dextran loops which was used for conjugating a protein, transferrin (Tf), known to be overexpressed on cancer cells' surface. Encapsulation of MM into NPs increased its cytotoxicity against HeLa cells at lower doses of MM than free MM. Additionally, the presence of conjugated Tf further increased the cytotoxicity of MM against HeLa cells as compared to non-conjugated NPs. Remarkably, both conjugated and non-conjugated MM loaded NPs were safe to normal cells (Vero and endometrial)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: An antibiotic adjuvant is a chemical substance used to modify or augment the effectiveness of primary antimicrobial agents against drug-resistant micro-organisms. Its use provides an alternative approach to address the global issue of antimicrobial resistance and enhance antimicrobial stewardship., Hypothesis/objectives: To determine the antimicrobial activity of a panel of potential antimicrobial adjuvants against common pathogens associated with canine otitis externa (OE)., Animals/isolates: A number of type strains and clinical isolates (n = 110) from canine OE were tested including Staphylococcus pseudintermedius, β-haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and Malassezia pachydermatis., Methods and Materials: Antimicrobial activities of monolaurin, monocaprin, N-acetylcysteine (NAC), polymyxin B nonapeptide, Tris-EDTA, Tris-HCL and disodium EDTA were tested using microdilution methodology according to CLSI guidelines., Results: N-acetylcysteine, Tris-EDTA and disodium EDTA had antimicrobial activity against both type strains and otic pathogens. The other adjuvants tested had limited to no efficacy. NAC had a minimal inhibitory concentration (MIC) range of 2,500-10,000 μg/mL for the various organisms. Pseudomonas aeruginosa isolates were eight times more susceptible to disodium EDTA in the presence of Tris-HCL in comparison to disodium EDTA alone. Malassezia pachydermatis isolates were most susceptible to Tris-EDTA (MIC 90  = 190/60 μg/mL) and disodium EDTA (MIC 90  = 120 μg/mL)., Conclusions and Clinical Relevance: N-acetylcysteine, Tris-EDTA and disodium EDTA have intrinsic antimicrobial activity and represent promising adjuvants that could be used to enhance the efficacy of existing antibiotics against Gram-negative and multidrug-resistant bacterial infections. These agents could be combined with other antimicrobial agents in a multimodal approach for mixed ear infections in dogs., (© 2018 ESVD and ACVD.)

Monoglycerides are esterified adducts of fatty acid and glycerol molecules that disrupt phospholipid membranes, leading to a wide range of biological functions such as antimicrobial activity. Among monoglycerides, glycerol monolaurate (GML) exhibits particularly high antimicrobial activity, although enzymatic hydrolysis of its ester group can diminish potency. Consequently, there have been efforts to identify more chemically stable versions of GML, most notably its alkylglycerol ether equivalent called dodecylglycerol (DDG). However, despite high structural similarity, biological studies indicate that DDG and GML are not functionally equivalent and it has been speculated that the two compounds might have different interaction profiles with phospholipid membranes. To address this outstanding question, herein, we employed supported lipid bilayer (SLB) platforms to experimentally characterize the interactions of DDG with phospholipid membranes. Quartz crystal microbalance-dissipation experiments identified that DDG causes concentration-dependent membrane morphological changes in SLBs and the overall extent of membrane remodeling events was greater than that caused by GML. In addition, time-lapsed fluorescence microscopy imaging experiments revealed that DDG causes extensive membrane tubulation that is distinct from how GML induces membrane budding. We discuss how differences in the head group properties of DDG and GML contribute to distinct membrane interaction profiles, offering insight into how the molecular design of DDG not only improves chemical stability but also enhances membrane-disruptive activity.