[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

Iva xanthiifolia leaf extract reduced the diversity of indigenous plant rhizosphere bacteria.

BACKGROUND: Iva xanthiifolia, native to North America, is now widely distributed in northeastern China and has become a vicious invasive plant. This article aims to probe the role of leaf extract in the invasion of I. xanthiifolia. METHODS: We collected the rhizosphere soil of Amaranthus tricolor and Setaria viridis in the invasive zone, the noninvasive zone and the noninvasive zone treated with extract from I. xanthiifolia leaf, and obtained I. xanthiifolia rhizosphere soil in the invasive zone. All wild plants were identified by Xu Yongqing. I. xanthiifolia (collection number: RQSB04100), A. tricolor (collection number: 831,030) and S. viridis (collection number: CF-0002-034) are all included in Chinese Virtual Herbarium ( https://www.cvh.ac.cn/index.php ). The soil bacterial diversity was analyzed based on the Illumina HiSeq sequencing platform. Subsequently, taxonomic analysis and Faprotax functional prediction were performed. RESULTS: The results showed that the leaf extract significantly reduced the diversity of indigenous plant rhizosphere bacteria. A. tricolor and S. viridis rhizobacterial phylum and genus abundances were significantly reduced under the influence of I. xanthiifolia or its leaf extract. The results of functional prediction showed that bacterial abundance changes induced by leaf extracts could potentially hinder nutrient cycling in native plants and increased bacterial abundance in the A. tricolor rhizosphere related to aromatic compound degradation. In addition, the greatest number of sensitive Operational Taxonomic Units (OTUs) appeared in the rhizosphere when S. viridis was in response to the invasion of I. xanthiifolia. It can be seen that A. tricolor and S. viridis have different mechanisms in response to the invasion of I. xanthiifolia. CONCLUSION: I. xanthiifolia leaves material has potential role in invasion by altering indigenous plant rhizosphere bacteria.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Cajanine promotes osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells.

BACKGROUND: Seed cells - mesenchymal stem cells (MSCs) - appear to be an attractive tool in the context of tissue engineering. Bone marrow represents the main source of MSCs for both experimental and clinical studies. However, the number limitation of bone marrow MSCs (BMSCs) and decreased function caused by proliferation make the search for adequate alternative sources of these cells for autologous and allogenic transplant necessary. OBJECTIVES: This study was aimed to investigate the roles of cajanine isolated from the extracts of Cajanus cajan L. Millsp. in the proliferation and differentiation of BMSCs, and to discover the mechanism of proliferation of BMSCs promoted by cajanine. MATERIAL AND METHODS: Bone marrow mesenchymal stem cells were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) and osteogenic differentiation was induced by adding dexamethasone, ascorbic acid and ß-glycerophosphate supplements. Bone marrow MSCs were cultured in medium without cajanine or supplemented with cajanine. The information about the proliferation and osteogenic differentiation of BMSCs was collated. The osteogenic differentiation potential of BMSCs was also assessed at the 3rd passage by Von Kossa staining. To observe cell signal transduction changes of BMSCs after culturing them with cajanine for 24 h, the western blot analysis was performed to detect phosphorylated cell cycle proteins and activated cyclins. RESULTS: After osteogenic induction, the differentiation of BMSCs was accelerated by cajanine treatment. Osteogenesis markers were upregulated by cajanine treatment at both protein and mRNA levels. Cajanine obviously promoted the proliferation of BMSCs. After BMSCs were cultured with cajanine for 24 h, the cell cycle regulator proteins were phosphorylated or upregulated. CONCLUSIONS: Cajanine can promote the expansion efficiency of BMSCs, at the same time keeping their multi-differentiation potential. Cajanine can activate the cell cycle signal transduction pathway, thus inducing cells to enter the G1/S phase and accelerating cells entering the G2/M phase. This study can contribute to the development of cajanine-based drugs in tissue engineering.