In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective:To investigate the effects of fibroblast growth factor receptor 1(FGFR1)on the resistance of colorectal cancer(CRC)cells to oxaliplatin(OXA).Methods:An OXA-resistant cell line(HCT8/OXA)was established by treating HCT8 CRC cells with low-dose OXA for a long period in vitro.The CCK-8 assay was used to compare the viability of the HCT8 and HCT8/OXA cells after OXA treatment and to exam-ine their resistance to the anticancer drug.Second-generation high-throughput sequencing technology was used to identify differentially ex-pressed genes between the parental and drug-resistant cells.The expression of FGFR1 in the HCT8 and HCT8/OXA cells was detected by Western blot assay.Colony formation and flow cytometric assays were used to determine cell proliferation and apoptosis,respectively.The expression of PI3K/AKT signaling pathway-related proteins was detected using Western blot assay.Results:Compared with the levels in the HCT8 cells,the FGFR1 levels were significantly increased in the HCT8/OXA cells(P<0.01).FGFR1 overexpression in the HCT8 cells increased their drug resistance(P<0.01)and proliferation(NC+OXA:236.67±6.24;FGFR1+OXA:568.33±6.24)and decreased their apoptotic rate after OXA treatment(NC+OXA:27.83±0.85;FGFR1+OXA:17.47±1.25).FGFR1 knockdown in the HCT8/OXA cells reduced their drug resistance(P<0.01)and proliferative ability(Si-NC+OXA:411±8.29;Si-FGFR1+OXA:233.33±20.55)and increased their apoptotic rate(Si-NC+OXA:2.85±0.17;Si-FGFR1+OXA:14.42±0.77).FGFR1 inhibited the activity of the PI3K/AKT signaling pathway and cell apoptosis and improved the proliferation and drug resistance of the CRC cells.By contrast,an activator of the PI3K/AKT pathway blocked the effects of FGFR1 on this sig-naling pathway and drug resistance in the CRC cells.Conclusions:FGFR1 can inhibit the PI3K/AKT signaling pathway and thereby reduce the sensitivity of CRC cells to OXA.

Objective:To investigate the effects of fibroblast growth factor receptor 1(FGFR1)on the resistance of colorectal cancer(CRC)cells to oxaliplatin(OXA).Methods:An OXA-resistant cell line(HCT8/OXA)was established by treating HCT8 CRC cells with low-dose OXA for a long period in vitro.The CCK-8 assay was used to compare the viability of the HCT8 and HCT8/OXA cells after OXA treatment and to exam-ine their resistance to the anticancer drug.Second-generation high-throughput sequencing technology was used to identify differentially ex-pressed genes between the parental and drug-resistant cells.The expression of FGFR1 in the HCT8 and HCT8/OXA cells was detected by Western blot assay.Colony formation and flow cytometric assays were used to determine cell proliferation and apoptosis,respectively.The expression of PI3K/AKT signaling pathway-related proteins was detected using Western blot assay.Results:Compared with the levels in the HCT8 cells,the FGFR1 levels were significantly increased in the HCT8/OXA cells(P<0.01).FGFR1 overexpression in the HCT8 cells increased their drug resistance(P<0.01)and proliferation(NC+OXA:236.67±6.24;FGFR1+OXA:568.33±6.24)and decreased their apoptotic rate after OXA treatment(NC+OXA:27.83±0.85;FGFR1+OXA:17.47±1.25).FGFR1 knockdown in the HCT8/OXA cells reduced their drug resistance(P<0.01)and proliferative ability(Si-NC+OXA:411±8.29;Si-FGFR1+OXA:233.33±20.55)and increased their apoptotic rate(Si-NC+OXA:2.85±0.17;Si-FGFR1+OXA:14.42±0.77).FGFR1 inhibited the activity of the PI3K/AKT signaling pathway and cell apoptosis and improved the proliferation and drug resistance of the CRC cells.By contrast,an activator of the PI3K/AKT pathway blocked the effects of FGFR1 on this sig-naling pathway and drug resistance in the CRC cells.Conclusions:FGFR1 can inhibit the PI3K/AKT signaling pathway and thereby reduce the sensitivity of CRC cells to OXA.