Hyaluronic acid fuels pancreatic cancer cell growth

Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in human PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not preclude the growth of human tumor xenografts in mice, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. We found that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles.

Polydopamine Doping and Pyrolysis of Cellulose Nanofiber Paper for Fabrication of Three-Dimensional Nanocarbon with Improved Yield and Capacitive Performances

Biomass-derived three-dimensional (3D) porous nanocarbons have attracted much attention due to their high surface area, permeability, electrical conductivity, and renewability, which are beneficial for various electronic applications, including energy storage. Cellulose, the most abundant and renewable carbohydrate polymer on earth, is a promising precursor to fabricate 3D porous nanocarbons by pyrolysis. However, the pyrolysis of cellulosic materials inevitably causes drastic carbon loss and volume shrinkage. Thus, polydopamine doping prior to the pyrolysis of cellulose nanofiber paper is proposed to fabricate the 3D porous nanocarbons with improved yield and volume retention. Our results show that a small amount of polydopamine (4.3 wt%) improves carbon yield and volume retention after pyrolysis at 700 °C from 16.8 to 26.4% and 15.0 to 19.6%, respectively. The pyrolyzed polydopamine-doped cellulose nanofiber paper has a larger specific surface area and electrical conductivity than cellulose nanofiber paper that without polydopamine. Owing to these features, it also affords a good specific capacitance up to 200 F g−1 as a supercapacitor electrode, which is higher than the recently reported cellulose-derived nanocarbons. This method provides a pathway for the effective fabrication of high-performance cellulose-derived 3D porous nanocarbons.

A Novel Functional Emulsifier Prepared with Modified Cassava Amylose with Octenyl Succinic Anhydride and Quercetin: Preparation and Application in the Pickering Emulsion

An emulsifier with a targeted antioxidant effect was prepared using the inclusion complexes of octenyl succinic anhydride (OSA)-modified cassava amylose (CA) and quercetin (Q). The designed emulsifier, a carbohydrate polymer-flavonoid complex, exhibited both amphiphilic and antioxidant properties. To investigate the physical and oxidation stabilities of the prepared emulsion, three types of emulsions were prepared: primary emulsions stabilized by enzyme-modified starch, secondary emulsions stabilized by OSA-CA, and tertiary emulsions stabilized by Q-encapsulated complexes (OSA-CA/Q). The structural characteristics of CA, OSA-CA, and OSA-CA/Q were investigated by scanning electron microscopy, Fourier transform infrared spectrometry, and small-angle X-ray scattering analysis. The stabilities of the emulsions were evaluated based on their particle size distribution, zeta potential, creaming stability, and peroxide value. The results showed that the secondary and tertiary emulsions exhibited a relatively narrower particle size distribution than the primary emulsions, but the particle size distribution of the tertiary emulsions was the narrowest (10.42 μm). Moreover, the secondary and tertiary emulsions had lower delamination indices than the primary emulsions after 7 days of storage. The results obtained from the antioxidant experiments indicated that OSA-CA/Q exhibited good oxidation stability for application in emulsion systems.

A new sugar for an old phage: A c-di-GMP dependent polysaccharide pathway sensitizes E. coli for bacteriophage infection

Bacteriophages are ubiquitous parasites of bacteria and major drivers of bacterial ecology and evolution. Despite an ever-growing interest in their biotechnological and therapeutic applications, detailed knowledge of the molecular mechanisms underlying phage-host interactions remains scarce. Here, we show that bacteriophage N4 exploits a novel surface glycan, NGR, as a receptor to infect its host Escherichia coli. We demonstrate that this process is regulated by the second messenger c-di-GMP and that N4 infection is specifically stimulated by the diguanylate cyclase DgcJ while the phosphodiesterase PdeL effectively protects E. coli from N4-mediated killing. PdeL-mediated protection requires its catalytic activity to reduce c-di-GMP and includes a secondary role as a transcriptional repressor. We demonstrate that PdeL binds to and represses the promoter of the wec operon, which encodes components of the ECA exopolysaccharide pathway. However, only the acetylglucosamine epimerase WecB but none of the other ECA components is required for N4 infection. Based on this, we postulate that NGR is an N-acetylmannosamine-based carbohydrate polymer that is produced and exported to the cell surface of E. coli in a c-di-GMP dependent manner where it serves as a receptor for N4. This novel carbohydrate pathway is conserved in E. coli and other bacterial pathogens, serves as the primary receptor for a range of N4-like bacteriophages, and is induced at elevated temperature and by specific amino acid-based nutrients. These studies provide an entry point into understanding how bacteria use specific regulatory mechanisms to balance costs and benefits of highly conserved surface structures.

Identifying the origin of local flexibility in a carbohydrate polymer

Correlating the structures and properties of a polymer to its monomer sequence is key to understanding how its higher hierarchy structures are formed and how its macroscopic material properties emerge. Carbohydrate polymers, such as cellulose and chitin, are the most abundant materials found in nature whose structures and properties have been characterized only at the submicrometer level. Here, by imaging single-cellulose chains at the nanoscale, we determine the structure and local flexibility of cellulose as a function of its sequence (primary structure) and conformation (secondary structure). Changing the primary structure by chemical substitutions and geometrical variations in the secondary structure allow the chain flexibility to be engineered at the single-linkage level. Tuning local flexibility opens opportunities for the bottom-up design of carbohydrate materials.

Fucoidan Extracted From Sporophyll of Undaria pinnatifida Grown in Weihai, China – Chemical Composition and Comparison of Antioxidant Activity of Different Molecular Weight Fractions

Fucoidan is a multifunctional marine carbohydrate polymer that differs in its chemical composition and bioactivity both between seaweed species and within species from different locations across the globe. In this study, fucoidan was extracted from the sporophyll of Undaria pinnatifida grown in Weihai, Shandong Province, China. Fucoidan fractions with molecular weight cutoffs (MWCO) of >300 kDa and <10 kDa were obtained via dialysis. The fucoidan standard from Sigma (Fstd, ≥95, CAS: 9072-19-9), fucoidan crude extract (WH), >300 kDa fraction (300k) and <10 kDa fraction (10k) were compared in terms of chemical composition and antioxidant capacity. Based on Fourier transform infrared spectroscopy (FT-IR) analysis, Fstd, WH, and 300k all showed strong bands around 830 cm−1, corresponding to the sulfate substituent in the molecule. The results showed that compared with WH and 300 k, the degree of sulfation at 10k was the lowest. From Nuclear magnetic resonance spectroscopy (NMR) result, the four fucoidan samples all contain α-L-fucose. The primary antioxidant ability of the 10k is significantly higher than that of the 300k, WH, and Fstd, but the secondary antioxidant capabilities of the 10k and 300k were similar, and both were higher than that of the butylated hydroxyanisole (BHA). The ferric reducing antioxidant ability was higher in the 300k and WH fractions. This demonstrates that fucoidan extracted from U. pinnatifida grown in Weihai, China should be a useful nutraceutical resource.

Investigation of antioxidant and anticancer activities of unsaturated oligo-galacturonic acids produced by pectinase of Streptomyces hydrogenans YAM1

Pectin, a diverse carbohydrate polymer in plants consists of a core of α-1,4-linked D-galacturonic acid units, includes a vast portion of fruit and agricultural wastes. Using the wastes to produce beneficial compounds is a new approach to control the negative environmental impacts of the accumulated wastes. In the present study, we report a pectinase producing bacterium Streptomyces hydrogenans YAM1 and evaluate antioxidative and anticancer effects of the oligosaccharides obtained from pectin degradation. The production of oligosaccharides due to pectinase activity was detected by thin layer chromatography (TLC) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results revealed that S. hydrogenans YAM1 can degrade pectin to unsaturated pectic oligo-galacturonic acids (POS) with approximately 93% radical scavenging activity in 20 mg/mL which it is more than 50% of the same concentration of pectin. Flow cytometric analysis revealed that MCF-7 cells viability decreased more than 32 and 92% following treatment with 6 and 20 mg/mL POS after 24 h, respectively. It is suggested that pectin degradation by S. hydrogenans YAM1 is not only a new approach to produce highly active compounds from fruit wastes, but also is an effective method to remove fibrous pollutants from different environments.

Alpha-Fetoprotein Binding Mucin and Scavenger Receptors: An Available Bio-Target for Treating Cancer

Alpha-fetoprotein (AFP) entrance into cancer cells is mediated by AFP receptors (AFPRs) and exerts malignant effects. Therefore, understanding the structure of AFPRs will facilitate the development of rational approaches for vaccine design, drug delivery, antagonizing immune suppression and diagnostic imaging to treat cancer effectively. Throughout the last three decades, the identification of universal receptors for AFP has failed due to their complex carbohydrate polymer structures. Here, we focused on the two types of binding proteins or receptors that may serve as AFPRs, namely, the A) mucin receptors family, and B) the scavenger family. We presented an informative review with detailed descriptions of the signal transduction, cross-talk, and interplay of various transcription factors which highlight the downstream events following AFP binding to mucin or scavenger receptors. We mainly explored the underlying mechanisms involved mucin or scavenger receptors that interact with AFP, provide more evidence to support these receptors as tumor AFPRs, and establish a theoretical basis for targeting therapy of cancer.