scholarly journals Digestion, fermentation, and pathogen anti-adhesive properties of the hMO-mimic di-fucosyl-β-cyclodextrin

2020 ◽  
Author(s):  
Stella A. Verkhnyatskaya ◽  
Chunli Kong ◽  
Cynthia Klostermann ◽  
Henk A. Schols ◽  
Paul de Vos ◽  
...  
Keyword(s):  
Human Milk ◽  
Biological Effects ◽  
Biological Evaluation ◽  
Intestinal Wall ◽  
Bioactive Molecules ◽  
Large Set ◽  
Adhesive Properties ◽  
Comprehensive Overview ◽  
E Coli ◽  
Decoy Effect

AbstractScopeHuman milk is widely acknowledged as the best food for infants, and that is not just because of nutritional features. Human milk also contains a plethora of bioactive molecules, including a large set of human milk oligosaccharides (hMOs). Especially fucosylated hMOs have received attention for their anti-adhesive effects on pathogens by preventing attachment to the intestinal wall. Because hMOs are generally challenging to produce in sufficient quantities to study and ultimately apply in (medical) infant formula, hMO mimics are interesting compounds to produce and evaluate for their biological effects.Methods and resultsWe investigated the digestion, fermentation, and pathogen anti-adhesive capacity of the novel hMO mimic di-fucosyl-β-cyclodextrin (DFβCD). We establish that DFβCD is not digested by α-amylase and also resists fermentation by the microbiota from a 9 month-old infant. In addition, we reveal that DFβCD blocks adhesion of enterotoxigenic E. coli (ETEC) to Caco-2 cells, especially when DFβCD is pre-incubated with ETEC prior to addition to the Caco-2 cells.ConclusionOur results suggests that DFβCD functions through a decoy effect. We expect that our results inspire the generation and biological evaluation of other fucosylated hMOs and mimics, to obtain a comprehensive overview of the anti-adhesive power of fucosylated glycans.

scholarly journals Digestion, fermentation, and pathogen anti-adhesive properties of the hMO-mimic di-fucosyl-β-cyclodextrin

2021 ◽  
Author(s):  
Stella A. Verkhnyatskaya ◽  
Chunli Kong ◽  
Cynthia E. Klostermann ◽  
Henk Schols ◽  
Paul de Vos ◽  
...  
Keyword(s):  
Human Milk ◽  
Bioactive Molecules ◽  
Adhesive Properties

Human milk is widely acknowledged as the best food for infants, and that is not just because of nutritional features. Human milk also contains a plethora of bioactive molecules, including...

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF 3-FORMYL INDOLE BASED SCHIFF BASES

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Singh Gurvinder ◽  
Singh Prabhsimran ◽  
Dhawan R. K.
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Analysis ◽  
Schiff Bases ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Fungal Strain ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Gram Negative ◽  
E Coli

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The  standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.

scholarly journals Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner
Keyword(s):  
Drug Delivery ◽  
Biological Effects ◽  
Invasive Technique ◽  
Stimuli Responsive ◽  
Comprehensive Overview ◽  
Drug Concentrations ◽  
Therapeutic Outcomes ◽  
Cost Efficient ◽  
Safety Considerations

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

scholarly journals Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

2021 ◽  
Vol 22 (14) ◽  
pp. 7631
Author(s):  
Lisa Wolff ◽  
Siva Sankar Murthy Bandaru ◽  
Elias Eger ◽  
Hoai-Nhi Lam ◽  
Martin Napierkowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Biological Effects ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Cancer Cell ◽  
Strand Breaks ◽  
Human Cancer Cell Lines

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

scholarly journals Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

2020 ◽  
Vol 32 (3) ◽  
pp. 580-586
Author(s):  
Ranjit V. Gadhave ◽  
Bhanudas S. Kuchekar
Keyword(s):  
Biological Evaluation ◽  
Bacterial Strains ◽  
Active Compounds ◽  
Design Synthesis ◽  
Structural Modifications ◽  
E Coli ◽  
Chemical Structures ◽  
Ft Ir ◽  
Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

scholarly journals Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn’s disease

2021 ◽  
pp. 118415
Author(s):  
Adeline Sivignon ◽  
Shin-Yi Yu ◽  
Nathalie Ballet ◽  
Pascal Vandekerckove ◽  
Nicolas Barnich ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesive Properties ◽  
E Coli

Microbial Growth Response to Hydrogel Encapsulated Quantum Dot Nanospheres

2007 ◽  
Vol 1064 ◽  
Author(s):  
Somesree GhoshMitra ◽  
Tong Cai ◽  
Santaneel Ghosh ◽  
Arup Neogi ◽  
Zhibing Hu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Growth Response ◽  
Microbial Growth ◽  
Biological Effects ◽  
Growth Curves ◽  
Swelling Properties ◽  
Growth Environment ◽  
E Coli ◽  
Cdte Qds ◽  
Biological Compatibility

ABSTRACTQuantum dots (QDs) are now used extensively for labeling in biomedical research due to their unique photoluminescence behavior, involving size-tunable emission color, a narrow and symmetric emission profile and a broad excitation range [1]. Uncoated QDs made of CdTe core are toxic to cells because of release of Cd2+ ions into the cellular environment. This problem can be partially solved by encapsulating QDs with polymers, like poly(N-isopropylacrylamide) (PNIPAM) or poly(ethylene glycol) (PEG). Based on biological compatibility, fast response as well as pH, temperature and magnetic field dependent swelling properties, hydrogel nanospheres has become carriers of drugs, fluorescence labels, magnetic particles for hyperthermia applications and particles that have strong optical absorption profiles for optical excitation. The toxicity of uncoated QDs are known; however, there have been a very limited number of studies specially designed to assess thoroughly the toxicity of nanosphere encapsulated QDs against QD density and dosing level.In this work, we present preliminary studies of biological effects of a novel QD based nanomaterial system on Escherichia coli (E. coli) bacteria. Cadmium chalcogenide QDs provide the most attractive fluorescence labels in comparison with routine dyes or metal complexes. Nanospheres on the other hand are the most commonly used carriers of fluorescence labels for fluorescence detection. The integration of fluorescent QDs in nanospheres therefore provides a new generation of fluorescence markers for biological assays. Hydrogels based on PNIPAM is a well known thermoresponsive polymer that undergoes a volume phase transition across the low critical solution (LCST) [2]. Therefore, the inherent temperature-sensitive swelling properties of PNIPAM offer the potentiality to control QD density within the nanospheres. In the present work, E. coli growth was monitored as E. coli served as a representation of how cells might respond in the presence of hydrogel encapsulated QDs in their growth environment. The present work describes the successful encapsulation of CdTe QDs in PNIPAM gel network. Microgel encapsulated QDs were synthesized by first preparing PNIPAM microspheres with cystaminebisacrylamide as a crosslinker and CdTe QDs capped with a stabilizer. The CdTe QDs were bonded into PNIPAM microgels through the replacement of CdTe's stabilizer inside PNIPAM microspheres. Growth curves were generated for E. coli growing in 20 mL of LB media containing hydrogel encapsulated QD nanospheres (400 nm diameter) at relatively higher (0.5mg/mL) and lower (0.01mg/mL) concentration of solution. From the growth curves, there was no evidence at lower concentration (0.01mg/mL) that the hydrogel encapsulated QDs prevent the microbial cells from growing but at higher concentration (0.5mg/mL), microbial growth was inhibited. Transmission Electron Microscopy (TEM) was used to characterize QD size and density inside the hydrogel nanospheres. Scanning Electron Microscopy (SEM) was used to observe size and morphology of the hydrogel particles. Further investigation is going on cell growth response at different QD density and to evaluate the limiting hydrogel concentration for different QD densities.

scholarly journals Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode

2021 ◽  
Author(s):  
Jonas Hauser ◽  
Edoardo Pisa ◽  
Alejandro Arias Vásquez ◽  
Flavio Tomasi ◽  
Alice Traversa ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Gut Microbiota ◽  
Human Milk ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Nervous System Development ◽  
Bioactive Molecules ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Eye Opening

AbstractBreastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

scholarly journals Monoclonal antibodies specific to a Ca2+-bound form of lipocortin I distinguish its Ca2+-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2

1990 ◽  
Vol 269 (3) ◽  
pp. 709-715 ◽  
Author(s):  
H Hayashi ◽  
M K Owada ◽  
S Sonobe ◽  
K Domae ◽  
T Yamanouchi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Phospholipase A2 ◽  
Inhibitory Activity ◽  
Biological Effects ◽  
Free Form ◽  
E Coli ◽  
Phospholipid Binding ◽  
Ef Hand

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

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