Pac-Man bacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an innovative Pac-Man imaging and therapy strategy, in which different bacteria displayed like Pac-Man actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~ 15.2-fold enhancement in photoacoustic signals and ~ 3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed Pac-Man strategy allows ultrasensitive imaging of as low as ~ 105 colony-forming unit (CFU) of bacteria in vivo, which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate Pac-Man strategy enables the detection of ~ 107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.

Metabolomics analysis of plasma and adipose tissue samples from mice orally administered with polydextrose and correlations with cecal microbiota

Polydextrose (PDX) is a branched glucose polymer, utilized as a soluble dietary fiber. Recently, PDX was found to have hypolipidemic effects and effects on the gut microbiota. To investigate these findings more closely, a non-targeted metabolomics approach, was exploited to determine metabolic alterations in blood and epididymal adipose tissue samples that were collected from C57BL/6 mice fed with a Western diet, with or without oral administration of PDX. Metabolomic analyses revealed significant differences between PDX- and control mice, which could be due to differences in diet or due to altered microbial metabolism in the gut. Some metabolites were found in both plasma and adipose tissue, such as the bile acid derivative deoxycholic acid and the microbiome-derived tryptophan metabolite indoxyl sulfate, both of which increased by PDX. Additionally, PDX increased the levels of glycine betaine and l-carnitine in plasma samples, which correlated negatively with plasma TG and positively correlated with bacterial genera enriched in PDX mice. The results demonstrated that PDX caused differential metabolite patterns in blood and adipose tissues and that one-carbon metabolism, associated with glycine betaine and l-carnitine, and bile acid and tryptophan metabolism are associated with the hypolipidemic effects observed in mice that were given PDX.

Chitosan and Wnt/β-catenin signaling pathway in different cancers

: It’s been a while since the disease of cancer was discovered in 16th and 17th century but still this disease is one of the most lethal diseases in the world which is taking a great number of lives every year. Cancer statistics suggest that there are still a lot of improvements that we have to make in the field of cancer treatment in order to overcome this deadly disease. Currently, nanotechnology has provided some more effective methods in this field which has attracted a lot of attention. Novel drug delivery systems which work through using nanoparticles might be the answer to many unsolved questions in treating cancer. Chitosan is a natural glucose polymer which has the potential to be utilized as a proper drug carrier by cause of its advantageous features. Chitosan-based delivery systems are able to affect cancerous cells in many pathways. Wnt signaling pathways which are one of the most essential ingredients of cancer pathogenesis, can be the target of chitosan nanoformulations. In this paper, we discussed the specific impacts of chitosan and its nanoformulations on each components of the Wnt/catenin pathway. Our conclusions might give novel insights for designing more efficient therapeutic approaches for several kinds of cancer.

Structure of the Mycobacterium smegmatis α-maltose-1-phosphate synthase GlgM

Mycobacterium tuberculosis produces glycogen (also known as α-glucan) to help evade human immunity. This pathogen uses the GlgE pathway to generate glycogen rather than the more well known glycogen synthase GlgA pathway, which is absent in this bacterium. Thus, the building block for this glucose polymer is α-maltose-1-phosphate rather than an NDP-glucose donor. One of the routes to α-maltose-1-phosphate is now known to involve the GlgA homologue GlgM, which uses ADP-glucose as a donor and α-glucose-1-phosphate as an acceptor. To help compare GlgA (a GT5 family member) with GlgM enzymes (GT4 family members), the X-ray crystal structure of GlgM from Mycobacterium smegmatis was solved to 1.9 Å resolution. While the enzymes shared a GT-B fold and several residues responsible for binding the donor substrate, they differed in some secondary-structural details, particularly in the N-terminal domain, which would be expected to be largely responsible for their different acceptor-substrate specificities.

Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer

Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 “sweet” taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1) detectable when both receptor subunits are absent and 2) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose.

Mixed drink increased carbohydrate oxidation but not performance during a 40 km time trial

Background: The present study aimed to determine whether consuming a glucose polymer (GP) and fructose would result in increased carbohydrate oxidation rates and improve 40 km time trial performance compared with an isocaloric GP-only drink.Methods: Eight well-trained male competitive cyclists (VO2max 62.7 ± 9.4 ml/kg/min, power output 5.1 ± 0.6 Watts/kg) participated in three visits consisting of a peak power output (Wmax) and VO2 max test and two separate visits of a 105 minute steady state ride (at 65% Wmax), followed by a 40 km time trial. Participants received 1.2 g/min of either a GP or mixed drink every 15 min.Results: No differences were found in the 40 km performance between GP (69:14 min ± 4.12, mean ± SD) and the mixed drink (66:58 min ± 4.51, mean ± SD) trials (p = 0.289). There were no differences in blood glucose or lactate between the trials. No differences in total oxidation were found in either carbohydrate or fat oxidation rates; however, exogenous carbohydrate oxidation was significantly different between the GP drink trials at t=90 min (GP: 0.96 ± 0.36 g/min; mixed drink: 1.53 ± 0.48 g/min; p = 0.041, mean ± SD).Conclusion: The present study found no improvement in 40 km time trial time between an isocaloric GP-only or a GP and fructose drink, and no differences in any of the measured variables other than exogenous carbohydrate oxidation at 90 minutes during the pre-time trial steady state ride.

Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis

♦BackgroundPeritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA).♦MethodsComputer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 – 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused.♦ResultsThe UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2).♦ConclusionsThe findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18–19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.

The fermentation of polydextrose in the large intestine and its beneficial effects

Polydextrose is a randomly bonded glucose polymer with a highly branched and complex structure. It resists digestion in the upper gastrointestinal tract and is partially fermented in the large intestine by the colonic microbes. Due to its complex structure, a plethora of microbes is required for the catabolism of polydextrose and this process occurs slowly. This gradual fermentation of polydextrose gives rise to moderate amounts of fermentation products, such as short chain fatty acids and gas. The production of these metabolites continues in the distal part of the colon, which is usually considered to be depleted of saccharolytic fermentation substrates. The fermentation of polydextrose modifies the composition of the microbiota in the colon, and has been shown to impact appetite and satiety in humans and improve the gastrointestinal function. The purpose of this short review is to summarise the in vitro, in vivo and human studies investigating the fermentation properties of polydextrose in the large intestine.