Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.

Complexes of Glucarolactones with Water-Soluble Copolymers of N-Vinylpyrrolidone with N-Vinylamine as Inhibitors of β-Glucuronidase Efficacy

Water-soluble complexes of N-vinylpyrrolidone/N-vinylamine copolymers with lactones of D-glucuronic acid were obtained and characterized by chromatographic, spectral, and hydrodynamic methods. The complexes efficiently inhibited the enzyme β-glucuronidase that causes the appearance of bladder tumors. The products demonstrated prolonged action and were stable during storage.

A Novel Polysaccharide Isolated From Fresh Longan (Dimocarpus longan Lour.) Activates Macrophage via TLR2/4-Mediated PI3/AKT and MyD88/TRAF6 Pathways

A novel immunomodulatory polysaccharide (LP4) with a molecular weight 6.31 × 104 g/mol was purified from fresh longan pulp. It was composed of mannose, glucose, glucuronic acid, galactose, xylose, arabinose, galacturonic acid, fucose, and rhamnose in a molar percentage of 36:31:10:7:4:4:3:2:2, and mainly linked by (1→6)-β-Man, (1→4)-β-Glc and (1→6)-α-Glc. LP4 can obviously enhance the phagocytosis of macrophages and promote the proliferation of lymphocytes. After treating macrophages with LP4 (12.5–50 μg/ml), the production of IL-1β and TNF-α was significantly increased. These increases of cytokines were suppressed when the TLR2/TLR4 receptors were inhibited by anti-TLR2 and/or anti-TLR4 antibodies. Moreover, the mRNA expression of INOS, AKT, PI3K, TRAF6 and MyD88 was significantly suppressed by TLR2/TLR4 antibodies. These results indicated that LP4 induced macrophage activation mainly via the TLR2 and TLR4-induced PI3K/AKT and MyD88/TRAF6 pathways.

Indirect Pathway Metabolic Engineering Strategies for Enhanced Biosynthesis of Hyaluronic Acid in Engineered Corynebacterium glutamicum

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and N-acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, Corynebacterium glutamicum, a safe GRAS (generally recognized as safe) host, was utilized and metabolically engineered previously. In this work, to achieve further enhancement of HA yield, four strategies were proposed and performed separately first, i.e., (1) improvement of glucose uptake via iolR gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes pgsA1/pgsA2/cls involved in cardiolipin synthesis; (3) duly expressed Vitreoscilla hemoglobin in genome, enhancing HA titer coupled with more ATP and improved NAD+/NADH (>7.5) ratio; and (4) identification of the importance of glutamine for HA synthesis through transcriptome analyses and then enhancement of the HA titer via its supplement. After that, we combined different strategies together to further increase the HA titer. As a result, one of the optimal recombinant strains, Cg-dR-CLS, yielded 32 g/L of HA at 60 h in a fed-batch culture, which was increased by 30% compared with that of the starting strain. This high value of HA titer will enable the industrial production of HA via the engineered C. glutamicum.

SYNTHESIS AND PROPERTIES OF MODIFIED XANTHAN GUM

Xanthan gum is widely used as a stabilizing, emulsifying, thickening agent in pharmacology, medicine, food, oil, paint, textile, perfume, mining and agriculture. For food purposes, potassium, sodium or calcium salts of xanthan formed by carboxyl groups of glucuronic acid and pyruvate group are used. Currently, xanthan gum is not produced on an industrial scale in Russia. There are repeated attempts to create industries in various regions of the country. The paper synthesizes hydrophobized acetylated xanthan gum derivatives with different degrees of substitution. Physical-chemical and colloidal-chemical properties of initial and modified gum are compared by methods of viscosimetry, tensiometry, IR spectroscopy. The point of zero charge of xanthan gum is determined.. Change of macromolecule conformation depending on pH of aqueous solution and preliminary dewatering is shown. Delamination temperatures of initial and modified forms of xanthan gum were determined. The critical micelle formation concentration of the modified gum is 0.2%. At this concentration, the surface activity of the gum is 6.1 and 7.9 mJ m/kg when replacing two and five hydroxo groups, respectively. The possibility of using modified xanthan gum as a binder for obtaining fuel pellets with improved operational properties and calorific value is shown.

Unraveling Synergism between Various GH Family Xylanases and Debranching Enzymes during Hetero-Xylan Degradation

Enzymes classified with the same Enzyme Commission (EC) that are allotted in different glycoside hydrolase (GH) families can display different mechanisms of action and substrate specificities. Therefore, the combination of different enzyme classes may not yield synergism during biomass hydrolysis, as the GH family allocation of the enzymes influences their behavior. As a result, it is important to understand which GH family combinations are compatible to gain knowledge on how to efficiently depolymerize biomass into fermentable sugars. We evaluated GH10 (Xyn10D and XT6) and GH11 (XynA and Xyn2A) β-xylanase performance alone and in combination with various GH family α-l-arabinofuranosidases (GH43 AXH-d and GH51 Abf51A) and α-d-glucuronidases (GH4 Agu4B and GH67 AguA) during xylan depolymerization. No synergistic enhancement in reducing sugar, xylose and glucuronic acid released from beechwood xylan was observed when xylanases were supplemented with either one of the glucuronidases, except between Xyn2A and AguA (1.1-fold reducing sugar increase). However, overall sugar release was significantly improved (≥1.1-fold reducing sugar increase) when xylanases were supplemented with either one of the arabinofuranosidases during wheat arabinoxylan degradation. Synergism appeared to result from the xylanases liberating xylo-oligomers, which are the preferred substrates of the terminal arabinofuranosyl-substituent debranching enzyme, Abf51A, allowing the exolytic β-xylosidase, SXA, to have access to the generated unbranched xylo-oligomers. Here, it was shown that arabinofuranosidases are key enzymes in the efficient saccharification of hetero-xylan into xylose. This study demonstrated that consideration of GH family affiliations of the carbohydrate-active enzymes (CAZymes) used to formulate synergistic enzyme cocktails is crucial for achieving efficient biomass saccharification.

Synthesis and Bioactivity of Ancorinoside B, A Marine Diglycosyl Tetramic Acid

The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-d-galactopyranosyl-(1→4)-β-d-glucuronic acid tethered to a d-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected d-lactose derived thioglycoside, its attachment to a C20-aldehyde spacer, functionalization of the latter with a terminal N-(β-ketoacyl)-d-aspartate, and a basic Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited multiple biological effects of medicinal interest. It inhibited the secretion of the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, and also the growth of Staphylococcus aureus biofilms by ca 87% when applied at concentrations as low as 0.5 µg/mL. This concentration is far below its MIC of ca 67 µg/mL and thus unlikely to induce bacterial resistance. It also led to a 67% dispersion of preformed S. aureus biofilms when applied at a concentration of ca 2 µg/mL. Ancorinoside B might thus be an interesting candidate for the control of the general hospital, catheter, or joint protheses infections.

Effect of fermentation time on the content of bioactive compounds with cosmetic and dermatological properties in Kombucha Yerba Mate extracts

Kombucha is a beverage made by fermenting sugared tea using a symbiotic culture of bacteria belonging to the genus Acetobacter, Gluconobacter, and the yeasts of the genus Saccharomyces along with glucuronic acid, which has health-promoting properties. The paper presents the evaluation of ferments as a potential cosmetic raw material obtained from Yerba Mate after different fermentation times with the addition of Kombucha. Fermented and unfermented extracts were compared in terms of chemical composition and biological activity. The antioxidant potential of obtained ferments was analyzed by evaluating the scavenging of external and intracellular free radicals. Cytotoxicity was determined on keratinocyte and fibroblast cell lines, resulting in significant increase in cell viability for the ferments. The ferments, especially after 14 and 21 days of fermentation showed strong ability to inhibit (about 40% for F21) the activity of lipoxygenase, collagenase and elastase enzymes and long‐lasting hydration after their application on the skin. Moreover, active chemical compounds, including phenolic acids, xanthines and flavonoids were identified by HPLC/ESI–MS. The results showed that both the analyzed Yerba Mate extract and the ferments obtained with Kombucha may be valuable ingredients in cosmetic products.