Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule’s study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.
Purpose: Therapeutic thorax irradiation as an intervention in lung cancer has its limitations due to toxic effects leading to pneumonitis and/or pulmonary fibrosis. It has already been confirmed that hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, is involved in inflammation disorders and wound healing in lung tissue. We examined the effects after gamma irradiation of hyaluronic acid nanoparticles (HANPs) applied into lung prior to that irradiation in a dose causing radiation-induced pulmonary injuries (RIPI). Materials and Methods: Biocompatible HANPs were first used for viability assay conducted on the J774.2 cell line. For in vivo experiments, HANPs were administered intratracheally to C57Bl/6 mice 30 min before thoracic irradiation by 17 Gy. Molecular, cellular, and histopathological parameters were measured in lung and peripheral blood at days 113, 155, and 190, corresponding to periods of significant morphological and/or biochemical alterations of RIPI. Results: Modification of linear hyaluronic acid molecule into nanoparticles structure significantly affected the physiological properties and caused long-term stability against ionizing radiation. The HANPs treatments had significant effects on the expression of the cytokines and particularly on the pro-fibrotic signaling pathway in the lung tissue. The radiation fibrosis phase was altered significantly in comparison with a solely irradiated group. Conclusions: The present study provides evidence that application of HANPs caused significant changes in molecular and cellular patterns associated with RIPI. These findings suggest that HANPs could diminish detrimental radiation-induced processes in lung tissue, thereby potentially decreasing the extracellular matrix degradation leading to lung fibrosis.
SUMMARY: The development of Streptomyces rimosus in submerged culture, in a medium containing starch, glucose, ammonium sulphate, corn-steep liquor and calcium carbonate, takes place in several phases which differ in their morphological and biochemical characteristics. The starting phase is characterized by the logarithmic growth of thick Gram-positive filaments of the primary mycelium. Nucleic acids and respiratory enzymes are being synthesized during this phase and free amino acids and inorganic phosphorus in the medium are being almost completely used up. A considerable amount of pyruvic acid is being produced and accumulated in the medium. No production of oxytetracycline and pigments takes place. In the phase of logarithmic growth the respiration of the culture reaches a maximum value of 500-700 ml. 02/l./hr. ; at this stage growth of the primary mycelium ceases and its hyphae undergo fragmentation. Pyruvic acid, which had accumulated in the medium in the phase of logarithmic growth, is rapidly used up during the fragmentation period. From the fragments of the primary mycelium long Gram-negative filaments of secondary mycelium start growing. Growth in this phase is accompanied neither by any significant increase of the respiration nor by excretion of pyruvic acid; deoxyribonucleic acid (DNA) synthesis is considerably slower than in the phase of logarithmic growth and the total amount of ribonucleic acid (RNA) is decreasing ; oxytetracycline and pigments are being produced both by the growing secondary mycelium and in the subsequent stationary phase.During the growth and development of actinomycetes morphological and physiological changes take place, both in surface cultures (Klieneberger-Nobel, 1947) and in submerged cultures (Carvajal, 1947;Biffi, Boretti, Di Marco & Pennella, 1954;Scotti & Zocchi, 1955;Baldacci, 1956). The development of the culture takes place in roughly two phases: in the first phase long hyphae develop from the spores; these hyphae undergo fragmentation or sporulation ; the fragments or spores give rise to the hyphae of the second generation. Similar morphological changes take place also during the growth of Streptomyces rimosus, a producer of the antibiotic oxytetracycline (ProkofievaBelgorskaya, Pestiereva & Rudaya, 1956). A biochemical characterization of the development of this species has so far not been presented; very little information is available especially about the factors which determine the existence and transition of the growth phases. Knowledge of these factors is important not only for our understanding of the physiology of the actinomycetes, but also from the practical standpoint; it enables us to predict the development of the culture and to control it by purposeful combinations of medium composition and other cultivation conditions. Knowledge of these factors which limit growth and determine the transition of one phase into the
During the biosynthetic production of chlortetracycline on a medium with sucrose, soy meal, corn steep extract, sodium chloride, ammonium sulphate, calcium carbonate and beet molasses, the amount of nucleic acids synthesized by the culture and the maximum respiration of the culture is determined by the amount of inorganic phosphate in the original medium. Chlortetracycline production does not start until all the inorganic phosphate has been consumed. The adverse influence of increased amounts of inorganic phosphate upon production of chlortetracycline is more apparent in flasks on a shaking machine than in agitated and aerated fermentation tanks with higher oxygen transfer numbers.
2GI
A d . Biochem. (Bioph!ys.). 25 (1950), 262Giorn. microbiol.,
(1958), 97
DEVELOPMENT OF STREPTOMYCES A [JREOFACIEXS
27113 DoskoEiI, J., Siliyta, B., l
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