scholarly journals Efficient production of high-molecular-weight hyaluronic acid with a two-stage fermentation

RSC Advances ◽  
2018 ◽  
Vol 8 (63) ◽  
pp. 36167-36171 ◽  
Author(s):  
J. Liu ◽  
Y. Wang ◽  
Z. Li ◽  
Y. Ren ◽  
Y. Zhao ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Control Strategy ◽  
Fermentation Process ◽  
High Level Synthesis ◽  
Efficient Production ◽  
Two Stage ◽  
High Level

A two-stage fermentation process with a segmented control strategy provides high-level synthesis in both HA titer and molecular weight.

scholarly journals Heterologous Production of Hyaluronic Acid in an ε-Poly-l-Lysine Producer, Streptomyces albulus

2015 ◽  
Vol 81 (11) ◽  
pp. 3631-3640 ◽  
Author(s):  
Tomohiro Yoshimura ◽  
Nobuyuki Shibata ◽  
Yoshimitsu Hamano ◽  
Kazuya Yamanaka
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Glucose Dehydrogenase ◽  
Efficient Production ◽  
Present System ◽  
Heterologous Production ◽  
Content Type ◽  
Wide Range ◽  
Lysine Producer ◽  
High Level

ABSTRACTHyaluronic acid (HA) is used in a wide range of medical applications, where its performance and therapeutic efficacy are highly dependent on its molecular weight. In the microbial production of HA, it has been suggested that a high level of intracellular ATP enhances the productivity and molecular weight of HA. Here, we report on heterologous HA production in an ε-poly-l-lysine producer,Streptomyces albulus, which has the potential to generate ATP at high level. ThehasAgene fromStreptococcus zooepidemicus, which encodes HA synthase, was refactored and expressed under the control of a late-log growth phase-operating promoter. The expression of the refactoredhasAgene, along with genes coding for UDP-glucose dehydrogenase, UDP-N-acetylglucosamine pyrophosphorylase, and UDP-glucose pyrophosphorylase, which are involved in HA precursor sugar biosynthesis, resulted in efficient production of HA in the 2.0 MDa range, which is greater than typical bacterial HA, demonstrating that a sufficient amount of ATP was provided to support the biosynthesis of the precursor sugars, which in turn promoted HA production. In addition, unlike in the case of streptococcal HA,S. albulus-derived HA was not cell associated. Based on these findings, our heterologous production system appears to have several advantages for practical HA production. We propose that the present system could be applicable to the heterologous production of a wide variety of molecules other than HA in the case their biosynthesis pathways require ATPin vivo.

Preparation and Characterization of the High Molecular Weight [3H]Hyaluronic Acid

1992 ◽  
Vol 57 (10) ◽  
pp. 2151-2156 ◽  
Author(s):  
Peter Chabreček ◽  
Ladislav Šoltés ◽  
Hynek Hradec ◽  
Jiří Filip ◽  
Eduard Orviský
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Methyl Bromide ◽  
High Performance ◽  
Hydrogen Atoms ◽  
Isolation And Characterization ◽  
Labelling Procedure ◽  
Enzymatic Depolymerization

Two methods for the preparation of high molecular weight [3H]hyaluronic acid were investigated. In the first one, hydrogen atoms in the molecule were replaced by tritium. This isotopic substitution was performed in aqueous solution using Pd/CaCO3 as the catalyst. In the second method, the high molecular weight hyaluronic acid was alkylated with [3H]methyl bromide in liquid ammonia at a temperature of -33.5 °C. High-performance gel permeation chromatographic separation method was used for the isolation and characterization of the high molecular weight [3H]hyaluronic acid. Molecular weight parameters for the labelled biopolymers were Mw = 128 kDa, Mw/Mn = 1.88 (first method) and Mw = 268 kDa, Mw/Mn = 1.55 (second method). The high molecular weight [3H]hyaluronic acid having Mw = 268 kDa was degraded further by specific hyaluronidase. Products of the enzymatic depolymerization were observed to be identical for both, labelled and cold biopolymer. This finding indicates that the described labelling procedure using [3H]methyl bromide does not induce any major structural rearrangements in the molecule.

Surface Modification of Ultra-High Molecular Weight Polyethylene with Crosslinked Hyaluronic Acid and its Antiwear Performance

2015 ◽  
Vol 642 ◽  
pp. 94-98
Author(s):  
Chau Chang Chou ◽  
Yu Hsiang Hao ◽  
Fu Yin Hsu
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Incident Light ◽  
Contact Angle Measurement ◽  
Angle Measurement ◽  
Coated Sample ◽  
Infrared Spectrometry ◽  
Water Contact ◽  
Ultra High Molecular Weight

The surface of high-pressure crystallized ultra-high molecular weight polyethylene (UHMWPE) was modified for application as an artificial cartilage material. A UHMWPE surface pretreated by a series of processes, including treatment with O2-plasma and ethylenediamine solution, was coated with hyaluronic acid (HA). After that, adipic acid dihydrazide (AAD) was added to partially crosslink the HA coating in order to enhance its durability. The modified samples were verified by water contact angle measurement and Fourier transform infrared spectrometry. Both HA layers, original and crosslinked, were also quantitatively evaluated by carbohydrate chemistry assay according to the absorbance of the incident light. The tribological performance of the samples was evaluated by a pin-on-disk test rig lubricated by normal saline under an average pressure of 18 MPa and at a sliding speed of 0.03 m/s for 45 h. The wear resistance of the HA-coated UHMWPE specimens promoted by the crosslink process was superior to that of the original HA-coated sample, and that resistance was maintained after immersion in saline solution for one month.

scholarly journals Az állkapocsízületi károsodás kezelése szteroiddal, illetve hialuronsavval

2018 ◽  
Vol 159 (36) ◽  
pp. 1475-1482 ◽  
Author(s):  
Szonja Vingender ◽  
László Restár ◽  
Krisztián Benedek Csomó ◽  
Péter Schmidt ◽  
Péter Hermann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Visual Analogue Scale ◽  
High Molecular Weight ◽  
Analogue Scale ◽  
Mouth Opening ◽  
Facial Region ◽  
Prolonged Effect ◽  
Maximal Mouth Opening ◽  
Invasive Intervention

Abstract: Introduction: Derangement of the temporomandibular joint complicates everyday life, due to the masticatory malfunction and the continuous pain sensation of the head and facial region. The therapy is multidisciplinary and varying. In case of the inefficiency of conservative therapy, minimally invasive intervention is needed with intraarticular injection. Aim: The aim of our study was to examine whether hyaluronic acid injection is more beneficial compared to corticosteroid in 37 joints. We also examined whether the efficacy of the therapy is influenced by hyaluronic acid molecular weight and the used protocol. Method: Wilkes stage, maximal mouth opening and the Visual Analogue Scale were determined pre-operatively and 6 months later. Corticosteroid application was performed once, hyaluronic acid was injected on a weekly bases 3 times in a row, by use of low (6–10 × 105 dalton) or high molecular weight (24–36 × 105 dalton) preparations. Results: The medical state of the patients treated with corticosteroid temporarily improved, but the symptoms returned. Due to hyaluronic acid treatment, significant improvement was revealed in all parameters (pwilkes<0.0001; pmouth-opening = 0.0002; pVAS<0.0001). There was no significant relapse (T = 2.05). The third administration of hyaluronic acid resulted in a significant improvement of the Visual Analogue Scale compared to the first and second injection (T3.–1. = 20.37; T3.–2. = 9.57). Conclusions: Comparing the two agents we can state that hyaluronic acid was significantly more effective and its application for three times seems to be the most effective treatment decreasing the symptoms. The high molecular weight solution was more effective in increasing mouth opening. In contrast to hyaluronic acid, corticosteroid had no prolonged effect in higher Wilkes stages. Orv Hetil. 2018; 159(36): 1475–1482.

Therapeutic Effects of High Molecular Weight Hyaluronic Acid in Severe Pseudomonas Aeruginosa Pneumonia in Ex Vivo Perfused Human Lungs

2021 ◽  
Author(s):  
Xiwen Zhang ◽  
Shinji Sugita ◽  
Airan Liu ◽  
Yoshifumi Naito ◽  
Wonjung Hwang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Weight ◽  
Pseudomonas Aeruginosa ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Bacterial Pneumonia ◽  
Ex Vivo ◽  
Therapeutic Effects ◽  
Human Lungs ◽  
Protein Permeability

Introduction: We previously reported that extracellular vesicles (EVs) released during Escherichia coli bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from Escherichia coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. Methods: For lungs with baseline alveolar fluid clearance (AFC)<10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (N = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC>10%/h, HMW HA 2 mg was injected intravenously after 1 h (N = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. Results: For lungs with AFC<10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC>10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation or bacterial counts. Discussion: In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.

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