Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer’s disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.

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Abstract. Associations of functional single nucleotide polymorphisms in MIF-173G/C with early stage cervical cancer were investigated in a hospital-based case-control study on 250 patients with cervical cancer prior to surgery (including 49 cases with and 201 cases without lymphatic metastasis) and 147 healthy controls. The polymorphism was assessed using restriction fragment length polymorphism polymerase chain reaction, and the MIF serum concentration was examined using the enzyme-linked immunosorbent assay to analyze the correlation between the polymorphism and the MIF serum concentration. Carriers of the variant C allele in MIF-173 were at a significantly higher risk of cervical cancer compared to carriers of the wild-type allele (aOR=1.508; 95% CI, 1.128-2.016, p=0.05). The GC and CC genotypes may be the causative factors for cervical cancer (aOR=1.851; 95% CI, 1.132-3.027, p=0.013). Individuals with the GC+CC genotype and C allele at the MIF-173G/C site were at a significantly higher risk of cervical cancer and lymphatic metastasis. The risk of lymphatic metastasis in early stage cervical cancer was increased more than 1.6 times in patients with the CC and GC genotypes compared with those with the GG genotype. The genotype distribution and allele frequency of MIF-173G/C were statistically significant in the well-, moderately and poorly differentiated groups (P<0.05). Compared to the GG genotype and G allele, patients with GC and CC genotypes and C allele exhibited a lower degree of differentiation and a higher degree of malignancy. A significant difference was observed in MIF serum concentrations among the various subgroups (P<0.05). The early cervical cancer, lymphatic metastasis and poorly differentiated groups exhibited higher MIF levels in serum. Moreover, patients with the CC genotype exhibited higher MIF serum concentration, which could increase the risk of early stage cervical cancer and lymphatic metastasis. The results presented in this study provide the first evidence that the genetic polymorphism MIF-173 is associated with cervical cancer in humans. Detection of MIF serum concentration and genotyping may be used as biomarkers for early diagnosis and therapy for cervical cancer.