IGF-1 exerts anti-apoptotic effects and promotes epithelial proliferation which is an important in the pathway to adenoma formation

In the last few years, CHIR-99021 mutants of Aspergillus tubingensis and Penicillium rugulosum with increased P solubilization ability were obtained by random mutation with UV light. Thus, the objective of this work was to select A. niger mutants with increased P solubilization capacity in the presence of F2. Additionally, the effect of mutagenesis on fungal processes involved in P solubilization was also evaluated, namely the production of organic acids and medium acidification. Mutagenesis using UV light allowed the generation of strains with increased P-solubilizing ability in the presence of F2. The most prominent phenotypic difference between the mutants and the WT was the profile of organic acids produced. Organic acids are effective agents in mobilizing P from RPs or soil particles due to their capacity to form chelates with cations linked to P in poorly soluble forms. However, the type of organic acids produced in a microbial solubilization system is of great importance, given that the effectiveness of an organic acid as a chelating agent is highly dependent on the chemical structure, type, and position of the carboxyl and hydroxyl groups in the molecule. The mutants FS1-331 and FS1-555 were the only ones that produced detectable quantities of oxalic acid in the medium with Araxa´ RP. The capacity to produce this acid under such conditions is probably one of the features that confer the superiority of these mutants over the WT at RP solubilization, since the production of gluconic and citric acids by the mutants was not higher than that of the WT. Previous works with the starting strain FS1 have already suggested the importance of oxalic acid for P solubilization. The lack of oxalic acid production by the WT in the present work is probably a consequence of the short incubation time adopted, which, in turn, highlights the efficiency of the mutants in producing this acid. Oxalic acid was reported as one of the most effective organic acid in releasing P from RPs. The chemical structure of oxalic acid is formed by the linkage of two carboxyl groups. The proximity of these carboxyl groups increases its chelation ability. Additionally, oxalate has a high tendency to precipitate with Ca2+, favoring the solubilization of apatite RPs. Nonetheless, there must be other factors besides oxalic acid production that are related to the superiority of the mutants. Depending on the chemical composition of RPs, another organic acid, e.g. citric acid, can be more effective in solubilizing P. Moreover, chemical elements released from RP can modulate the metabolism of each fungal strain, which could explain the differences between mutants in solubilizing different P sources. Acromegaly is a chronic disease resulting from excessive secretion of growth hormone and insulin-like growth factor-1. IGF-1 promotes mitosis and suppresses apoptosis of cells by binding to the IGF-1 receptor b, and is thought to be responsible for the increased risk of developing malignancies, mainly colorectal, breast, prostate, and hematologic. Several studies have reported a high frequency of thyroid cancer mostly papillary thyroid cancer in patients with acromegaly. The reported prevalence is 4.7–11%, which is much higher than that in the general population. However, the actual incidence of thyroid cancer in patients with acromegaly and the impact of active acromegaly on the development of thyroid cancer is unknown due to the relative rarity of the condition. Although controversy remains regarding general cancer risk, higher rates of colon cancer in patients with acromegaly compared to the general population have been reported.

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