Jang, Y.-J. | bioRxiv Science

bioRxiv2023

Evaluation of purine-nucleoside degrading ability and in vivo uric acid lowering of Streptococcus thermophilus (ID-PDP3), a novel antiuricemia strain

This study evaluated 15 lactic acid bacteria in terms of their ability to degrade inosine and hypoxanthine--which are the intermediates in purine metabolism--for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, CR1 (Lactiplantibacillus plantarum) and GZ1 (Lactiplantibacillus pentosus) showed the highest nucleoside degrading rates and were therefore selected for further characterization. IDCC 2201 (S. thermophilus), which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected. These three selected strains were examined in terms of the effect of probiotics on lowering serum uric acid in a rat model of potassium oxonate (PO)-induced hyperuricemia. Among them, the level of serum uric acid was most reduced by IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of IDCC 2201 recovered the ratio of Bacteroidetes/Firmicutes in the intestinal microbial composition unbalanced by hyperuricemia and showed a difference in the intestinal microbial composition compared to the group administered with allopurinol. Moreover, intestinal short-chain fatty acids (SCFAs) were significantly increased. Ultimately, the findings show that IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and restores intestinal flora and SCFAs, ultimately suggesting that IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.

microbiology↗

bioRxiv2019

GV1001 prevents ovarian follicle loss triggered by an anti-VEGF monoclonal antibody targeting non-small cell lung carcinoma xenografts in mice

Premature ovarian failure (POF) that could result from chemotherapy applied to young female cancer patients is a significant challenge in reproductive biology. It is widely believed that the hyperactivation of dormant primordial follicles following chemotherapy is a leading cause of POF, but it remains unclear how therapeutic cues are generated and transduced into follicular activation. Here, we provide evidence that supports that GV1001, an immunotherapeutic peptide targeting telomerase, plays a role in the deterrence of POF in mice. In vivo non-small cell lung carcinoma (NSCLC) tumor xenografts were produced by inoculating NSCLC cells into the flank of BALB/c female athymic mice and then subjected to cancer chemotherapy with GV1001 and bevacizumab, an anti-cancer antibody drug, humanized anti-VEGF monoclonal antibody. Bevacizumab when administered at the dosage of 5 mg/kg for three weeks was effective in inhibiting growth of NSCLC tumor xenografts, and its anti-cancer efficacy was not interfered by the presence of GV1001. As expected, bevacizumab induced follicular loss by accelerating primordial follicle growth into primary or secondary follicles concomitant with a decline of serum antimullerian hormone (AMH) level and deactivation of Foxo3 signaling as evidenced by immunohistochemical and immunofluorescent assessment. However, bevacizumab-induced follicle stimulating effects were mitigated by GV1001 co-administration as evidenced by the analysis of follicular count, serum AMH level, and Foxo3a expression. From this study, we propose that a combinatorial administration of GV1001 and bevacizumab could deter POF of young female cancer patients without hampering the anti-cancer effectiveness of bevacizumab.

pharmacology and toxicology↗