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BioRxiv : the Preprint Server For... May 2024Solid tumors harbor immunosuppressive microenvironments that inhibit tumor infiltrating lymphocytes (TILs) through the voracious consumption of glucose. We sought to...
Solid tumors harbor immunosuppressive microenvironments that inhibit tumor infiltrating lymphocytes (TILs) through the voracious consumption of glucose. We sought to restore TIL function by providing them with an exclusive fuel source. The glucose disaccharide cellobiose, which is a building block of cellulose, contains a β-1,4-glycosidic bond that cannot be hydrolyzed by animals (or their tumors), but fungal and bacterial organisms have evolved enzymes to catabolize cellobiose and use the resulting glucose. By equipping T cells with two proteins that enable import and hydrolysis of cellobiose, we demonstrate that supplementation of cellobiose during glucose withdrawal restores T cell cytokine production and cellular proliferation. Murine tumor growth is suppressed and survival is prolonged. Offering exclusive access to a natural disaccharide is a new tool that augments cancer immunotherapies. Beyond cancer, this approach could be used to answer questions about the regulation of glucose metabolism across many cell types, biological processes, and diseases.
PubMed: 38826342
DOI: 10.1101/2024.05.20.595053 -
BMC Plant Biology Jun 2024Vegetable soybean is an important vegetable crop in world. Seed size and soluble sugar content are considered crucial indicators of quality in vegetable soybean, and... (Comparative Study)
Comparative Study
BACKGROUND
Vegetable soybean is an important vegetable crop in world. Seed size and soluble sugar content are considered crucial indicators of quality in vegetable soybean, and there is a lack of clarity on the molecular basis of grain quality in vegetable soybean.
RESULTS
In this context, we performed a comprehensive comparative transcriptome analysis of seeds between a high-sucrose content and large-grain variety (Zhenong 6, ZN6) and a low-sucrose content and small-grain variety (Williams 82, W82) at three developmental stages, i.e. stage R5 (Beginning Seed), stage R6 (Full Seed), and stage R7 (Beginning Maturity). The transcriptome analysis showed that 17,107 and 13,571 differentially expressed genes (DEGs) were identified in ZN6 at R6 (vs. R5) and R7 (vs. R6), respectively, whereas 16,203 and 16,032 were detected in W82. Gene expression pattern and DEGs functional enrichment proposed genotype-specific biological processes during seed development. The genes participating in soluble sugar biosynthesis such as FKGP were overexpressed in ZN6, whereas those responsible for lipid and protein metabolism such as ALDH3 were more enhanced in W82, exhibiting different dry material accumulation between two genotypes. Furthermore, hormone-associated transcriptional factors involved in seed size regulation such as BEH4 were overrepresented in ZN6, exhibiting different seed size regulation processes between two genotypes.
CONCLUSIONS
Herein, we not only discovered the differential expression of genes encoding metabolic enzymes involved in seed composition, but also identified a type of hormone-associated transcriptional factors overexpressed in ZN6, which may regulate seed size and soluble content. This study provides new insights into the underlying causes of differences in the soybean metabolites and appearance, and suggests that genetic data can be used to improve its appearance and textural quality.
Topics: Glycine max; Seeds; Gene Expression Profiling; Edible Grain; Transcriptome; Genes, Plant; Gene Expression Regulation, Plant; Genotype; Sucrose
PubMed: 38825702
DOI: 10.1186/s12870-024-05214-1 -
Chemical Senses Jan 2024This study examined how olfaction impacts ingestive responses of mice to sugar solutions. Experiment 1 asked whether naïve C57BL/6 (B6) mice could identify 1 M glucose,...
This study examined how olfaction impacts ingestive responses of mice to sugar solutions. Experiment 1 asked whether naïve C57BL/6 (B6) mice could identify 1 M glucose, fructose, or sucrose solutions based on odor cues, during a 30-min 2-bottle acceptability test. We tested mice both before and after they were rendered anosmic with ZnSO4 treatment. We used 2 indirect measures of odor-mediated response: number of trials initiated and latency to initiate licking. Before ZnSO4 treatment, the mice learned how to identify 1 M glucose and fructose (but not sucrose) solutions based on odor cues. ZnSO4 treatment eliminated their ability to identify the glucose and fructose solutions. Experiment 2 asked whether 2 d of exposure to a 1 M glucose, fructose, or sucrose solution improved the identification of the same sugar solution. Following exposure, the B6 mice identified all 3 sugar solutions based on odor cues. Experiment 3 asked whether T1R3 knockout mice (i.e. mice lacking the T1R3 subunit of the T1R2 + R3 sweet taste receptor) could learn to discriminate 0.44 M glucose and fructose solutions based on odor cues. All mice were subjected to a 1-h preference test, both before and after exposure to the 0.44 M glucose and fructose solutions. During exposure, the experimental mice received ZnSO4 treatment, whereas the control mice received saline treatment. Before exposure, neither type of mouse preferred the glucose solution. After exposure, the control mice preferred the glucose solution, whereas the experimental mice did not. Our results reveal that mice can learn to use odor cues to identify and discriminate between sugar solutions.
Topics: Animals; Odorants; Mice; Mice, Inbred C57BL; Cues; Male; Smell; Sucrose; Fructose; Mice, Knockout; Glucose; Zinc Sulfate; Female; Sugars; Receptors, G-Protein-Coupled
PubMed: 38824409
DOI: 10.1093/chemse/bjae024 -
Carbohydrate Polymers Sep 2024Arabinoxylan is a major hemicellulose in the sugarcane plant cell wall with arabinose decorations that impose steric restrictions on the activity of xylanases against...
Arabinoxylan is a major hemicellulose in the sugarcane plant cell wall with arabinose decorations that impose steric restrictions on the activity of xylanases against this substrate. Enzymatic removal of the decorations by arabinofuranosidases can allow a more efficient arabinoxylan degradation by xylanases. Here we produced and characterized a recombinant Bifidobacterium longum arabinofuranosidase from glycoside hydrolase family 43 (BlAbf43) and applied it, together with GH10 and GH11 xylanases, to produce xylooligosaccharides (XOS) from wheat arabinoxylan and alkali pretreated sugarcane bagasse. The enzyme synergistically enhanced XOS production by GH10 and GH11 xylanases, being particularly efficient in combination with the latter family of enzymes, with a degree of synergism of 1.7. We also demonstrated that the enzyme is capable of not only removing arabinose decorations from the arabinoxylan and from the non-reducing end of the oligomeric substrates, but also hydrolyzing the xylan backbone yielding mostly xylobiose and xylose in particular cases. Structural studies of BlAbf43 shed light on the molecular basis of the substrate recognition and allowed hypothesizing on the structural reasons of its multifunctionality.
Topics: Oligosaccharides; Glycoside Hydrolases; Glucuronates; Endo-1,4-beta Xylanases; Xylans; Saccharum; Cellulose; Bifidobacterium longum; Hydrolysis; Substrate Specificity; Recombinant Proteins; Disaccharides
PubMed: 38823916
DOI: 10.1016/j.carbpol.2024.122248 -
Carbohydrate Polymers Sep 2024Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin... (Review)
Review
Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.
Topics: Heparin, Low-Molecular-Weight; Humans; Quality Control; Animals; Anticoagulants
PubMed: 38823901
DOI: 10.1016/j.carbpol.2024.122216 -
Food Research International (Ottawa,... Jul 2024Excessive intake of sugar has become a public concern. However, it is challenging for food industries to decrease sugar level without sacrificing safety and sensory...
Excessive intake of sugar has become a public concern. However, it is challenging for food industries to decrease sugar level without sacrificing safety and sensory profile. Odor-induced sweetness enhancement (OISE) is believed to be a novel and promising strategy for sugar reduction. In order to investigate the OISE effect of mango aroma and evaluate its degree of sugar reduction in low-sugar beverages, a mathematical model was constructed through sensory evaluation in this study. The results showed that the maximum liking of low-sugar model beverages was 4.28 % sucrose and 0.57 % mango flavor. The most synergistic of OISE was at the concentration level of 2.24 % sucrose + 0.25 % mango flavor, which was equivalent to 2.96 % pure sucrose solution. With 32.14 % sugar reduction, the mango aroma was suggested to generate the OISE effect. However, the same level of garlic aroma was not able to enhance sweetness perception, suggesting that the congruency of aroma and taste is a prerequisite for the OISE effect to occur. This study demonstrated that the cross-modal interaction of mango aroma on sweetness enhancement in low-sugar model beverages could provide practical guidance for developing sugar-reduced beverages without applying sweeteners.
Topics: Humans; Odorants; Mangifera; Female; Adult; Male; Young Adult; Taste; Sweetening Agents; Smell; Sucrose; Consumer Behavior; Beverages; Taste Perception; Flavoring Agents
PubMed: 38823860
DOI: 10.1016/j.foodres.2024.114451 -
International Journal of Biological... Jun 2024The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically...
The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca was not always conducive to structure formation, and excessive Ca addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca and DE. All of these results showed that Ca addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.
Topics: Pectins; Malus; Rheology; Sucrose; Calcium; Viscosity; Gels; Esterification; Water
PubMed: 38821787
DOI: 10.1016/j.ijbiomac.2024.132397 -
International Journal of Pharmaceutics Jun 2024The influence of hydroxypropyl cellulose type (HPC-SSL SFP, HPC-SSL), concentration (2 %, 3.5 %, 5 %) and filler (lactose, calcium hydrogen phosphate...
The influence of hydroxypropyl cellulose type (HPC-SSL SFP, HPC-SSL), concentration (2 %, 3.5 %, 5 %) and filler (lactose, calcium hydrogen phosphate (DCP)/microcrystalline cellulose (MCC)) on twin-screw wet granulation and subsequent tableting was studied. The aim was to identify the formulation of the highest tabletability which still fulfills the requirements of the disintegration. Lactose combined with 5 % binder enabled a higher tabletability and a faster disintegration than DCP/MCC. It was found that tabletability of lactose formulations can be increased by higher binder concentration and higher compression pressure while tabletability of DCP/MCC formulations can be only increased by higher compression pressure. It was observed that batches containing DCP/MCC failed the disintegration test, if the highest binder concentration and the highest compression pressure were used. To ensure a fast disintegration, the compression pressure or at least the binder concentration had to be low. Changing the disintegrant and its localization improved the DCP/MCC formulation, resulting in faster disintegration than lactose tablets. However, it also resulted in a lower tabletability. In this study best tablets were achieved with 3.5 % or 5 % binder and lactose as filler. These tablets presented the highest tabletability but still disintegrated in less than 500 s.
Topics: Tablets; Cellulose; Lactose; Excipients; Drug Compounding; Calcium Phosphates; Chemistry, Pharmaceutical; Pressure; Solubility
PubMed: 38821435
DOI: 10.1016/j.ijpharm.2024.124290 -
Applied Microbiology and Biotechnology May 2024Whey is a byproduct of dairy industries, the aqueous portion which separates from cheese during the coagulation of milk. It represents approximately 85-95% of milk's... (Review)
Review
Whey is a byproduct of dairy industries, the aqueous portion which separates from cheese during the coagulation of milk. It represents approximately 85-95% of milk's volume and retains much of its nutrients, including functional proteins and peptides, lipids, lactose, minerals, and vitamins. Due to its composition, mainly proteins and lactose, it can be considered a raw material for value-added products. Whey-derived products are often used to supplement food, as they have shown several physiological effects on the body. Whey protein hydrolysates are reported to have different activities, including antihypertensive, antioxidant, antithrombotic, opioid, antimicrobial, cytomodulatory, and immuno-modulatory. On the other hand, galactooligosaccharides obtained from lactose can be used as prebiotic for beneficial microorganisms for the human gastrointestinal tract. All these compounds can be obtained through physicochemical, microbial, or enzymatic treatments. Particularly, enzymatic processes have the advantage of being highly selective, more stable than chemical transformations, and less polluting, making that the global enzyme market grow at accelerated rates. The sources and different products associated with the most used enzymes are particularly highlighted in this review. Moreover, we discuss metagenomics as a tool to identify novel proteolytic enzymes, from both cultivable and uncultivable microorganisms, which are expected to have new interesting activities. Finally enzymes for the transformation of whey sugar are reviewed. In this sense, carbozymes with ß-galactosidase activity are capable of lactose hydrolysis, to obtain free monomers, and transgalactosylation for prebiotics production. KEY POINTS: • Whey can be used to obtain value-added products efficiently through enzymatic treatments • Proteases transform whey proteins into biopeptides with physiological activities • Lactose can be transformed into prebiotic compounds using ß-galactosidases.
Topics: Whey Proteins; Protein Hydrolysates; Prebiotics; Humans; Whey; Lactose; beta-Galactosidase
PubMed: 38819482
DOI: 10.1007/s00253-024-13117-2 -
Chemistry (Weinheim An Der Bergstrasse,... May 2024The Gal(α1-3)Gal is the terminal disaccharide unit of the α-Gal epitope [Gal(α1-3)Gal(β1-4)GlcNAc], an exogenous antigenic determinant with several clinical...
The Gal(α1-3)Gal is the terminal disaccharide unit of the α-Gal epitope [Gal(α1-3)Gal(β1-4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non-primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the α-Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers-shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(α1-3)Gal disaccharide of the α-Gal antigen.
PubMed: 38818641
DOI: 10.1002/chem.202401771