Modification of the Antibiotic, Colistin, with Dextrin Causes Enhanced Cytotoxicity and Triggers Apoptosis in Myeloid Leukemia.

Introduction: Acute myeloid leukemia (AML) remains difficult to treat due to its heterogeneity in molecular landscape, epigenetics and cell signaling alterations. Precision medicine is a major goal in AML therapy towards developing agents that can be used to treat patients with different 'subtypes' in combination with current chemotherapies. We have previously developed dextrin-colistin conjugates to combat the rise in multi-drug resistant bacterial infections and overcome dose-limiting nephrotoxicity. Recent evidence of colistin's anticancer activity, mediated through inhibition of intracellular lysine-specific histone demethylase 1 (LSD1/KDM1A), suggests that dextrin-colistin conjugates could be used to treat cancer cells, including AML. This study aimed to evaluate whether dextrin conjugation (which reduces in vivo toxicity and prolongs plasma half-life) could enhance colistin's cytotoxic effects in myeloid leukemia cell lines and compare the intracellular uptake and localization of the free and conjugated antibiotic. Results: Our results identified a conjugate (containing 8000 g/mol dextrin with 1 mol% succinoylation) that caused significantly increased toxicity in myeloid leukemia cells, compared to free colistin. Dextrin conjugation altered the mechanism of cell death by colistin, from necrosis to caspase 3/7-dependent apoptosis. In contrast, conjugation via a reversible ester linker, instead of an amide, had no effect on the mechanism of the colistin-induced cell death. Live cell confocal microscopy of fluorescently labelled compounds showed both free and dextrin-conjugated colistins were endocytosed and co-localized in lysosomes, and increasing the degree of modification by succinoylation of dextrin significantly reduced colistin internalization. Discussion: Whilst clinical translation of dextrin-colistin conjugates for the treatment of AML is unlikely due to the potential to promote antimicrobial resistance (AMR) and the relatively high colistin concentrations required for anticancer activity, the ability to potentiate the effectiveness of an anticancer drug by polymer conjugation, while reducing side effects and improving biodistribution of the drug, is very attractive, and this approach warrants further investigation.

Integrated Analysis of Gut Microbiome and Adipose Transcriptome Reveals Beneficial Effects of Resistant Dextrin from Wheat Starch on Insulin Resistance in Kunming Mice.

Systemic chronic inflammation is recognized as a significant contributor to the development of obesity-related insulin resistance. Previous studies have revealed the physiological benefits of resistant dextrin (RD), including obesity reduction, lower fasting glucose levels, and anti-inflammation. The present study investigated the effects of RD intervention on insulin resistance (IR) in Kunming mice, expounding the mechanisms through the gut microbiome and transcriptome of white adipose. In this eight-week study, we investigated changes in tissue weight, glucose-lipid metabolism levels, serum inflammation levels, and lesions of epididymal white adipose tissue (eWAT) evaluated via Hematoxylin and Eosin (H&E) staining. Moreover, we analyzed the gut microbiota composition and transcriptome of eWAT to assess the potential protective effects of RD intervention. Compared with a high-fat, high-sugar diet (HFHSD) group, the RD intervention significantly enhanced glucose homeostasis (e.g., AUC-OGTT, HOMA-IR, p < 0.001), and reduced lipid metabolism (e.g., TG, LDL-C, p < 0.001) and serum inflammation levels (e.g., IL-1ß, IL-6, p < 0.001). The RD intervention also led to changes in the gut microbiota composition, with an increase in the abundance of probiotics (e.g., Parabacteroides, Faecalibaculum, and Muribaculum, p < 0.05) and a decrease in harmful bacteria (Colidextribacter, p < 0.05). Moreover, the RD intervention had a noticeable effect on the gene transcription profile of eWAT, and KEGG enrichment analysis revealed that differential genes were enriched in PI3K/AKT, AMPK, in glucose-lipid metabolism, and in the regulation of lipolysis in adipocytes signaling pathways. The findings demonstrated that RD not only ameliorated IR, but also remodeled the gut microbiota and modified the transcriptome profile of eWAT.

Combined resistant dextrin and low-dose Mg oxide administration increases short-chain fatty acid and lactic acid production by gut microbiota.

The consumption of resistant dextrin improves constipation, while its fermentation and degradation by the intestinal microbiota produce short-chain fatty acids (SCFA) and lactic acid, which have beneficial effects on host metabolism and immunity. Mg oxide (MgO) is an important mineral that is used to treat constipation. Therefore, resistant dextrin and MgO are often administered together to improve constipation. However, limited information is available regarding the effect of this combination on SCFA and lactic acid production. Crl:CD1(ICR) mice were fed a Mg-free diet with 5% resistant dextrin, followed by oral administration of MgO. We collected the cecum contents and measured SCFA and lactic acid levels. Additionally, the human subjects received resistant dextrin and Mg supplements as part of their habitual diet. The results of this study demonstrate that intestinal microbiota cannot promote SCFA and lactic acid production in the absence of Mg. In a mouse model, low doses of MgO promoted the production of SCFA and lactic acid, whereas high doses decreased their production. In humans, the combined consumption of resistant dextrin and Mg supplements increased the production of SCFA and lactic acid. The production of SCFA and lactic acid from dietary fiber may be augmented by the presence of MgO.

Effect of Resistant Dextrin on Intestinal Gas Homeostasis and Microbiota.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production.

Effects of Resistant Dextrin from Potato Starch on the Growth Dynamics of Selected Co-Cultured Strains of Gastrointestinal Bacteria and the Activity of Fecal Enzymes.

Preparations of resistant dextrins have become an interesting topic of research due to their properties, which bear resemblance those of prebiotics, e.g., the improvement of metabolic parameters, increased efficiency of the immune system and induction of vitamin production. The aim of this study was to investigate the effects of the resistant dextrin produced from potato starch on the growth dynamics of typical gastrointestinal microbiota and the activity of fecal enzymes in order to assess a possible exhibition of prebiotic properties. In the study, in vitro cultivation of co-cultures of Lactobacillus, Bifidobacterium, E. coli, Enterococcus, Clostridium and Bacteroides spp. was conducted on media enriched with the resistant dextrin. The CFU/mL for each strain was measured in time periods of 24, 48, 72, 96 and 168 h. Furthermore, the activities of α-glucosidase, α-galactosidase, ß-glucosidase, ß-galactosidase and ß-glucuronidase were determined using spectrophotometric methods at a wavelength of 400 nm. The results show that the resistant dextrin can be utilized as a source of carbon for the growth of intestinal bacteria. Moreover, the results revealed that, after 168 h of cultivation, it enhances the viability of probiotic strains of Lactobacillus and Bifidobacterium spp. and decreases the growth of other intestinal strains (Clostridium, Escherichia coli, Enterococcus and Bacteroides), which is demonstrated by a high Prebiotic Index (p < 0.05). Furthermore, there was no significant change in the pH of the cultures; however, the pace of the pH decrease during the cultivation was slower in the case of culture with resistant dextrin. Furthermore, it was revealed that usage of the resistant dextrin as a medium additive noticeably lowered the activities of ß-glucosidase and ß-glucuronidase compared to the control (p < 0.05), whereas the activities of the other fecal enzymes were affected to a lesser degree. The resistant dextrins derived from potato starch are a suitable prebiotic candidate as they promote the growth of beneficial strains of gut bacteria and improve health markers, such as the activity of fecal enzymes. Nevertheless, additional in vivo research is necessary to further assess the suspected health-promoting properties.

Diet Supplementation with NUTRIOSE, a Resistant Dextrin, Increases the Abundance of Parabacteroides distasonis in the Human Gut.

SCOPE: An imbalance of the gut microbiota ("dysbiosis") is associated with numerous chronic diseases, and its modulation is a promising novel therapeutic approach. Dietary supplementation with soluble fiber is one of several proposed modulation strategies. This study aims at confirming the impact of the resistant dextrin NUTRIOSE (RD), a soluble fiber with demonstrated beneficial health effects, on the gut microbiota of healthy individuals. METHODS AND RESULTS: Fifty healthy women are enrolled and supplemented daily with either RD (n = 24) or a control product (n = 26) during 6 weeks. Characterization of the fecal metagenome with shotgun sequencing reveals that RD intake dramatically increases the abundance of the commensal bacterium Parabacteroides distasonis. Furthermore, presence in metagenomes of accessory genes from P. distasonis, coding for susCD (a starch-binding membrane protein complex) is associated with a greater increase of the species. This suggests that response to RD might be strain-dependent. CONCLUSION: Supplementation with RD can be used to specifically increase P. distasonis in gut microbiota of healthy women. The magnitude of the response may be associated with fiber-metabolizing capabilities of strains carried by subjects. Further research will seek to confirm that P. distasonis directly modulates the clinical effects observed in other studies.

Diverse prebiotic effects of isomaltodextrins with different glycosidic linkages and molecular weights on human gut bacteria in vitro.

Isomaltodextrin (IMD) is a novel dietary fiber enzymatically produced by reconstructing the molecular chain structure of starch using glycosyltransferases. In this study, the specific prebiotic effects of α-1,6 linear and α-1,2 or α-1,3 branched IMDs with different molecular weights (Mw) on human intestinal bacteria were investigated by pure culture of single strains and mixed fermentation of human fecal microflora in vitro. The results showed that α-1,6 linear IMDs markedly promoted beneficial Bifidobacterium and Lactobacillus in both pure culture and mixed fermentation. α-1,3 branching exhibited similar selectivity with α-1,6 linkage but yielded more butyrate in pure cultures. In contrast, IMDs containing α-1,2 branches were utilized efficiently only during mixed fermentation, which was speculated to result from metabolic cross-feeding. Regarding Mw, IMDs with lower Mw showed better prebiotic effects in pure cultures but no differences in mixed culture. These findings provide a theoretical basis for their application as functional foods.

An alcohol-free beer enriched with isomaltulose and a resistant dextrin modulates gut microbiome in subjects with type 2 diabetes mellitus and overweight or obesity: a pilot study.

We aimed to study the effect of consuming an alcohol-free beer with modified carbohydrates composition (almost completely eliminating maltose and adding isomaltulose (16.5 g day-1) and resistant maltodextrin (5.28 g day-1)) in gut microbiome, compared to regular alcohol-free beer in subjects with T2DM or prediabetes and overweight/obesity. This is a pilot, randomized, double-blinded, crossover study including a sub-sample of a global study with 14 subjects: (a) consuming 66 cl day-1 of regular alcohol-free beer for the first 10 weeks and 66 cl day-1 of modified alcohol-free beer for the next 10 weeks; (b) the same described intervention in opposite order. BMI homogeneously decreased after both interventions. Glucose and HOMA-IR significantly decreased just after the participants consumed modified alcohol-free beer. These findings were in the same line as those reported in the global study. Dominant bacteria at baseline were Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes. Parabacteroides, from the Porphymonadaceae family, resulted as the feature with the greatest difference between beers (ANCOM analysis, W = 15). Feature-volatility analysis confirmed the importance of Parabacteroides within the model. Alcohol-free beers consumption resulted in an enhancement of pathways related to metabolism according to PICRUSt analysis, including terpenoid-quinone, lipopolysaccharides and N-glycan biosynthesis. Thus, an alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and the addition of maltodextrin within meals significantly impacts gut microbiota in diabetic subjects with overweight or obesity. This could, at least partially, explain the improvement in insulin resistance previously found after taking modified alcohol-free alcohol.Clinical Trial Registration: Registered under ClinicalTrials.gov identifier no. NCT03337828.

Glucagon-like peptide-1 response to whey protein is less diminished by dipeptidyl peptidase-4 in comparison with responses to dextrin, a lipid and casein in rats.

Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2-4 g/kg), but not by that of dextrin (2-4 g/kg), in control rats (untreated Sprague-Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague-Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response.

Effect of an alcohol-free beer enriched with isomaltulose and a resistant dextrin on insulin resistance in diabetic patients with overweight or obesity.

BACKGROUND & AIMS: The quality of carbohydrates has an essential role in nutritional management of type 2 diabetes mellitus (T2DM) because of its substantial impact on glucose homeostasis. Alcohol-free beer has beneficial bioactive components but it has a relatively high glycemic-index so its consumption is restricted in diabetic subjects. We aimed to explore the effect of an alcohol-free beer with modified carbohydrate composition almost completely eliminating maltose and adding isomaltulose (16.5 g/day) and a resistant maltodextrin (5.28 g/day) in comparison to a regular alcohol-free beer on glycemic control of diabetic subjects with overweight or obesity. DESIGN: We randomized 41 subjects into two groups: a) consumption of 66 cL/day of; regular alcohol-free beer for the first 10 weeks and 66 cL/day of alcohol-free beer with modified carbohydrate composition for the next 10 weeks; b) the same described intervention in opposite order. There was a washout period for 6-8 weeks between the two interventions. Participants were counseled to adhere to a healthy diet for cardiovascular health and to increase physical activity. Clinical, biochemical, anthropometric, lifestyle and satiety assessments were performed at the beginning and at the end of each period. RESULTS: Subjects showed significantly weight loss after the two ten weeks periods (-1.69 ± 3.21% and -1.77 ± 3.70% after experimental and regular alcohol-free beers, respectively, P = 0.881). Glucose and glycated hemoglobin did not significantly change after any period. Insulin concentrations and HOMA-IR significantly decreased (-11.1 [-21.3-4.64]% and -1.92 ± 32.8% respectively) after the intake of experimental alcohol-free beer but not after regular alcohol-free beer. Reductions remained statistically significant after adjusting for weight loss, energy intake, physical activity and intervention order. Subjects reported higher satiety scores after consuming experimental alcohol-free beer. CONCLUSIONS: An alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and the addition of a resistant maltodextrin within meals led to an improvement in insulin resistance in subjects with T2DM and overweight or obesity. CLINICAL TRIAL REGISTRATION: The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT03337828).

Oral intake of slowly digestible α-glucan, isomaltodextrin, stimulates glucagon-like peptide-1 secretion in the small intestine of rats.

To investigate whether oral intake of highly branched α-glucan isomaltodextrin (IMD) could stimulate ileal glucagon-like peptide-1 (GLP-1) secretion, we examined (1) the digestibility of IMD, (2) the digestion and absorption rates of IMD, in rat small intestine and (3) portal GLP-1 concentration in rats given IMD. In Expt 1, ileorectostomised rats were given a 3 % IMD diet for 10 d. Separately, a 16-h in vitro digestion of IMD, using porcine pancreatic α-amylase and brush-border membrane vesicles from rat small intestine, was conducted. In Expt 2, upon 24-h fasting, rats were given any of glucose, IMD and high-amylose maize starch (HAMS) (1 g/kg of body weight). In Expt 3, caecectomised rats were given 0·2 % neomycin sulphate and a 5 % IMD diet for 10 d. The in vivo and in vitro digestibility of IMD was 70-80 %. The fraction of IMD digested in vitro for the first 120 min was 67 % of that in maize starch. The AUC for 0-120 min of plasma glucose concentration was significantly lower in HAMS group and tended to be lower in IMD group than in the glucose group. Finally, we also observed that, when compared with control rats, glucose of IMD significantly stimulated and improved the concentration of portal active GLP-1 in antibiotic-administered, caecectomised rats. We concluded that IMD was slowly digested and the resulting glucose stimulated GLP-1 secretion in rat small intestine. Oral delivery of slowly released IMD glucose to the small intestine probably exerts important, yet unknown, physiological effects on the recipient.

The effect of resistant dextrin as a prebiotic on metabolic parameters and androgen level in women with polycystic ovarian syndrome: a randomized, triple-blind, controlled, clinical trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common abnormalities in women of reproductive age that can lead to a variety of metabolic and reproductive disorders. Studies reveal that a healthy diet is the most effective way for treating the risk factors associated with metabolic disorders and place greater emphasis on the consumption of prebiotic foods. The present study aims to determine the effect of resistant Dextrin on metabolic parameters, including lipid profile, fasting blood glucose (FBS) and high sensitivity C-reactive protein (hsCRP), and androgen levels, including serum levels of dehydroepiandrosterone sulfate (DHEA-S) and free testosterone, as the primary outcomes, and manifestations of PCOS including menstrual cycle irregularity and hirsutism, as the secondary outcomes. METHODS: This randomized, controlled, triple-blind, clinical trial was conducted on 62 women aged 18-45 in Tabriz, Iran, in 2016-2017. The participants were divided into a prebiotic group and a placebo group using block randomization. The prebiotic group consumed 20 g of resistant dextrin dissolved in a glass of water and the placebo group 20 g of maltodextrin also dissolved in a glass of water on a daily basis for 3 months. To measure the serum lipid profile, FBS, hsCRP, DHEA-S and free testosterone before and 3 months after the intervention, 5-ml blood samples were collected from the participants and analyzed using the ELISA method. The Ferriman-Gallwey scale for assessing hirsutism and a checklist for assessing menstrual cycle characteristics were completed before and 3 months after the intervention. A general linear model was used to analyze the data. RESULTS: No statistically significant differences were observed between the two groups in terms of sociodemographic characteristics and baseline values. 3 months after the intervention, based on the ANCOVA and after adjusting for the baseline values, the mean serum levels of LDL-C (adjusted mean difference = - 29.79; 95% CI = - 43.37 to - 16.21; P < 0.001), triglyceride (AMD = - 38.50; 95% CI = - 59.73 to - 17.28; P = 0.001), total cholesterol (AMD = - 29.98; 95% CI = - 40.14 to - 19.82; P < 0.001), FBS (AMD = - 11.24; 95% CI = - 15.43 to - 7.06; P < 0.001), hsCRP (AMD = - 1.75; 95% CI = - 2.92 to - 0.57; P = 0.004), DHEA-S (AMD = - 0.7; 95% CI = - 1.34 to - 0.13; P = 0.017) and free testosterone (AMD = - 0.32; 95% CI = - 0.56 to - 0.08; P = 0.010) revealed a statistically significant decrease in the intervention group compared to the placebo group, while the mean serum HDL-C showed a statistically significant increase in this group compared to the placebo group (AMD = 5.82; 95% CI = 2.27-9.37; P = 0.002). 3 months after the intervention, there was a significant difference between the two groups in terms of menstrual cycle intervals and hirsutism (P < 0.001). CONCLUSION: Resistant dextrin consumption can regulate metabolic parameters and androgen levels and manifestations including hirsutism and menstrual cycle irregularity in women with PCOS.

Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

SCOPE: The objective of the present study is to evaluate the effects of milk powder co-supplemented with inulin and resistant dextrin (MPCIR) on elderly patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A randomized, double-blind, placebo-controlled clinical trial is carried out among elderly T2DM patients. The subjects recruited from the community are randomly assigned to either the MPCIR group or placebo group for 12 weeks intervention. Each group receives 45 g milk powder with or without inulin and resistant dextrin. Anthropometric and metabolic variables are measured. For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mm Hg (p < 0.001, vs placebo group), respectively. Compared with the placebo group, the fasting and 2-h postprandial plasma glucose levels, glycosylated serum protein, and insulin resistance index of the MPCIR group are significantly decreased by 0.96 mmol L-1 , 1.47 mmol L-1 , 16.33 µmol L-1 , and 0.65 respectively (p < 0.001). The MPCIR group shows an increase by 7.09 µIU mL-1 and 20.43 in 2-h postprandial insulin (p = 0.016) and ß-cell function index (p < 0.001), respectively. CONCLUSION: MPCIR supplementation helps to improve glycemic control, insulin resistance, and blood pressure.

Hypoglycemic Effects of Pyrodextrins with Different Molecular Weights and Digestibilities in Mice with Diet-Induced Obesity.

Pyrodextrin shares some properties of resistant starch, which is metabolically beneficial, and has potential applications as a functional food. In this study, we report that the oral administration of pyrodextrin (50 mg/kg/d for 7 weeks) decreased blood glucose (from 9.18 ± 1.47 to 7.67 ± 0.42 mmol/L), serum HbA1c, triglycerides, adipocyte size, and body weight (from 24.4 ± 1.2 to 22.5 ± 1.2 g) in mice with high-fat-diet-induced obesity. Western-blotting analysis suggested that pyrodextrins decreased intestinal SGLT-1 and GLUT-2 expression to ∼70 and ∼60% of the obese control, respectively, which slowed down glucose transportation from the gut into the blood and tentatively improved hepatic metabolism. Moreover, the pyrodextrin with a lower molecular weight of 44 kDa, a more branched structure, and increased nondigestible starch of 46.2 ± 0.3% showed stronger hypoglycemic activity. This work provides important information for developing pyrodextrins as a functional food and dietary supplement for the management of obesity and diabetes.

Evaluation of a Spray-type, Novel Dextrin Hydrogel Adhesion Barrier Under Laparoscopic Conditions in a Porcine Uterine Horn Adhesion Model.

STUDY OBJECTIVE: To establish a porcine uterine horn adhesion model that mimicked laparoscopic procedures and use it to investigate the effect of a spray-type, novel dextrin hydrogel adhesion barrier (AdSpray; Terumo Corporation, Tokyo, Japan) on postsurgical adhesions. DESIGN: A single-blind randomized controlled trial (Canadian Task Force Classification I). SETTING: A Certified animal research facility. SUBJECTS: Sixteen female pigs. INTERVENTIONS: All animals underwent laparoscopically assisted adhesion-inducing surgery. The uterine horns and the peritoneum of the pelvic sidewall were injured. In the experimental group, AdSpray was applied to the injured site, and the handling of the sprayer was assessed. At 28 ± 1 days after surgery, animals were sacrificed, and adhesions at the injured site were evaluated. Uterine horn suture sites were examined under a light microscope to assess healing of the incised wound, the inflammatory reaction, abscess, and the foreign body reaction to the surgical suture. MEASUREMENTS AND MAIN RESULTS: The control group showed severe adhesions over the entire surface interface at the uterine horn suture sites and peritoneal resection site. Compared with the control treatment, AdSpray exhibited a higher percentage of adhesion-free sites (p < .001) and reduced the total adhesion score (p < .001). In the AdSpray group, no inflammation or abscess formation was observed on histopathological examination, and ideal healing of the suture sites was confirmed in all cases. CONCLUSION: Based on the results of the present study, the novel dextrin hydrogel shows excellent adhesion prevention and can be easily applied during laparoscopy using a dedicated sprayer.

Iodine-lithium-alpha-dextrin (ILαD) against Staphylococcus aureus skin infections: a comparative study of in-vitro bactericidal activity and cytotoxicity between ILαD and povidone-iodine.

BACKGROUND: As antimicrobial resistance continues to increase, revisiting old antimicrobial agents, modified to enhance efficacy and safety, becomes important. Iodine has been widely used for more than 150 years as a wound and skin disinfectant; it is an effective broad range bactericide and does not promote the development of resistant strains. The most important iodine-based agent is povidone-iodine (PVP-I) which provides excellent antibacterial activity. However, its safety profile has been questioned. AIM: To evaluate the in-vitro antibacterial efficacy and kinetic properties of a novel iodine-based compound, iodine lithium alpha-dextrin (ILαD), against Staphylococcus aureus, and compare the in-vitro cytotoxicity profiles of ILαD and PVP-I. METHODS: A minimum inhibitory concentration (MIC) microbroth dilution method was performed against 12 meticillin-resistant (MRSA) and eight meticillin-susceptible (MSSA) S. aureus clinical isolates using ILαD and PVP-I. Time-kill and post-antibiotic effect studies of ILαD provided rate-of-kill information. MTT cytotoxicity assays were performed using three cell lines, treated with MIC doses of ILαD and PVP-I. FINDINGS: The MIC values of ILαD and PVP-I against the MRSA strains were 125 mg/L and 31.25 mg/L, respectively. Time-kill and post-antibiotic effect studies of ILαD revealed a log10 reduction factor of 3 within 8 h of exposure at a 2 × MIC dose; the post-antibiotic effect was calculated at 5±0.3h. Cell viability was affected slightly at the MIC dose of ILαD, while the MIC dose of PVP-I exerted a strong cell growth inhibitory effect of 90-95%. CONCLUSIONS: ILαD could be a promising solution against staphylococcal infections as it is effective, does not promote the development of resistant strains, and in-vitro testing indicates that it may be safer than PVP-I. Further studies are justified to determine whether ILαD overcomes the clinical limitations of PVP-I.

Mechanistic Study of Utilization of Water-Insoluble Saccharomyces cerevisiae Glucans by Bifidobacterium breve Strain JCM1192.

Bifidobacteria exert beneficial effects on hosts and are extensively used as probiotics. However, due to the genetic inaccessibility of these bacteria, little is known about their mechanisms of carbohydrate utilization and regulation. Bifidobacterium breve strain JCM1192 can grow on water-insoluble yeast (Saccharomyces cerevisiae) cell wall glucans (YCWG), which were recently considered as potential prebiotics. According to the results of 1H nuclear magnetic resonance (NMR) spectrometry, the YCWG were composed of highly branched (1→3,1→6)-ß-glucans and (1→4,1→6)-α-glucans. Although the YCWG were composed of 78.3% ß-glucans and 21.7% α-glucans, only α-glucans were consumed by the B. breve strain. The ABC transporter (malEFG1) and pullulanase (aapA) genes were transcriptionally upregulated in the metabolism of insoluble yeast glucans, suggesting their potential involvement in the process. A nonsense mutation identified in the gene encoding an ABC transporter ATP-binding protein (MalK) led to growth failure of an ethyl methanesulfonate-generated mutant with yeast glucans. Coculture of the wild-type strain and the mutant showed that this protein was responsible for the import of yeast glucans or their breakdown products, rather than the export of α-glucan-catabolizing enzymes. Further characterization of the carbohydrate utilization of the mutant and three of its revertants indicated that this mutation was pleiotropic: the mutant could not grow with maltose, glycogen, dextrin, raffinose, cellobiose, melibiose, or turanose. We propose that insoluble yeast α-glucans are hydrolyzed by extracellular pullulanase into maltose and/or maltooligosaccharides, which are then transported into the cell by the ABC transport system composed of MalEFG1 and MalK. The mechanism elucidated here will facilitate the development of B. breve and water-insoluble yeast glucans as novel synbiotics.IMPORTANCE In general, Bifidobacterium strains are genetically intractable. Coupling classic forward genetics with next-generation sequencing, here we identified an ABC transporter ATP-binding protein (MalK) responsible for the import of insoluble yeast glucan breakdown products by B. breve JCM1192. We demonstrated the pleiotropic effects of the ABC transporter ATP-binding protein in maltose/maltooligosaccharide, raffinose, cellobiose, melibiose, and turanose transport. With the addition of transcriptional analysis, we propose that insoluble yeast glucans are broken down by extracellular pullulanase into maltose and/or maltooligosaccharides, which are then transported into the cell by the ABC transport system composed of MalEFG1 and MalK. The mechanism elucidated here will facilitate the development of B. breve and water-insoluble yeast glucans as novel synbiotics.

Effects of In Ovo feeding of dextrin-iodinated casein in broilers: I. Hatch weights and early growth performance.

This study was conducted to determine the effect of in ovo feeding of dextrin (Dext) and iodinated casein (IC) on hatch and early growth in broilers. Three experiments were conducted at a commercial hatchery using a commercial Inovoject™ system with treatments occurring in conjunction with vaccination at transfer from incubator to hatcher units (18.5 to 19 d embryonic development). In all 3 experiments, approximately 15,000 eggs (2,500 eggs per group) were treated and transferred to a single hatcher unit. Treatments in Exp. 1 consisted of buffered saline solution alone (Control, Cont) or a dextrin solution (Dext, 18% maltodextrin, 10% potato starch dextrin) containing zero, 80, 240, 720, or 2,160 µg IC/mL. The results of this initial experiment indicated that broiler chicks at hatch that received 240 and 720 µg IC/mL in Dext were heavier (P < 0.05) compared to the other treatment groups; there were no differences in hatchability between groups. Based on these findings, subsequent studies used treatments of zero, 240, and 480 µg/mL IC in Dext or Cont. In Exp. 2, hatch weights in all treatment groups were higher (P < 0.05) compared to those receiving Cont. In Exp. 3, chicks given Dext alone or 240 and 480 µg/mL in saline weighed less at hatch compared to the other treatment groups. However, chicks provided Dext alone in Exp. 3 had less weight loss after a 24-hour holding period compared to the other groups. All treatment groups exhibited greater weight gain from one to 10 d compared to the Cont group. The results indicate that in ovo feeding of broiler embryos with Dext containing 240 and 480 µg IC/mL may have beneficial effects on broiler hatch weights and early growth rate.

Effect of in ovo feeding of dextrin-iodinated casein in broilers: II. Hatch window and growth performance.

Studies were conducted using a commercial InovojectTM system to determine effects of in ovo feeding of dextrin and iodinated casein (IC) on hatch and posthatch growth in broilers. At ∼18.5 d embryonic development, eggs were treated with 0, 240, or 480 µg IC/mL in saline (Cont, IC240, and IC480) or dextrin (Dext, DextIC240 and DextIC480). The Dext solution consisted of 18% maltodextrin and 10% potato starch dextrin; saline was the vehicle used by the company for in ovo vaccination. The volume for all in ovo treatments was 50 µL/injection. Eggs in Experiment 1 were transferred to a commercial hatcher unit whereas eggs in Experiments 2 and 3 were transferred to a research hatcher unit to assess effects of treatments on timing of hatch. At hatch, chicks were randomly selected and placed in floor pens and grown to 6 wk. In Experiment 1, there were no differences in hatch weights, but broilers provided Dext IC240 in ovo were heavier (P < 0.05) at 6 wk compared to other treatments with the exception of the Dext IC240 group. In Experiment 2, hatch weights were heavier (P < 0.05) in chicks receiving IC240 and DexIC480 treatments compared to Controls. At 6 wk, broilers in all treatments were heavier (P < 0.05) than Cont with the exception of IC480. In Experiment 3, hatch was stimulated by IC240 (in saline), but was delayed by Dext IC240. Serum analysis of ß-hydroxybutyrate (µM/mL), as an indicator of ketone accumulation from fat metabolism of chicks held in chick boxes for 24 h posthatch (to simulate delay in placement after hatch), indicated that chicks in the IC240 group (that hatched earlier) had higher blood ketones compared to chicks that received Dext or DextIC240 in ovo (that hatched later). We conclude dextrin and iodinated casein (240 µg/mL) provided in ovo (∼18.5 d of embryonic development) has the potential to improve chick quality and posthatch body weight by delaying or narrowing hatch window.

Synthesis of multivalent sialyllactosamine-carrying glyco-nanoparticles with high affinity to the human influenza virus hemagglutinin.

A series of multivalent sialoglyco-conjugated nanoparticles were efficiently synthesized by using highly-branched α-glucuronic acid-linked cyclic dextrins (GlcA-HBCD) as a backbone. The sialoglycoside-moieties, with varying degrees of substitution, could be incorporated onto the preformed nanoparticles. These synthesized particles, which are highly soluble in aqueous solution, were shown to have a spherical nanostructure with a diameter of approximately 15nm. The interactions of the sialoglyco-nanoparticles (Neu5Acα2,6LacNAc-GlcA-HBCDs) with human influenza virus strain A/Beijing/262/95 (H1N1) were investigated using a hemagglutination inhibition assay. The sialoglyco-nanoparticle, in which the number of sialic acid substitution is 30, acted as a powerful inhibitor of virus binding activity. We show that both distance and multiplicity of effective ligand-virus formation play important roles in enhancing viral inhibition. Our results indicate that the GlcA-HBCD backbone can be used as a novel spherical nanocluster material for preparing a variety of glyco-nanoparticles to facilitate molecular recognition.