Mollugin suppresses proliferation and drives ferroptosis of colorectal cancer cells through inhibition of insulin-like growth factor 2 mRNA binding protein 3/glutathione peroxidase 4 axis.

Increasing researches have demonstrated that targeting ferroptosis might be a new conceptual avenue to treat colorectal cancer (CRC). Mollugin is a phytochemical isolated from Rubia cordifolia L. with antitumor activity. However, whether ferroptosis mediates the antitumor activity of mollugin in CRC has not been explored. Our study aims to investigate the antitumor and pro-ferroptosis effects, and mechanisms of mollugin in CRC. We found that mollugin led to ferroptosis in CRC cells, resulting in reduced GSH level and elevated levels of ROS, Fe2+, and MDA. Mollugin treatment caused obvious decrease in cell viability and proliferation in CRC cells, which were aggravated by ferroptosis inducer erastin and attenuated by ferroptosis inhibitor ferrostatin-1. Tumor xenografts experiments proved that mollugin suppressed the tumor growth, while treatment with ferrostatin-1 attenuated the antitumor activity of mollugin in vivo. Integrated bioinformatics analysis showed that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) was highly expressed in CRC tissues and indicated poor prognosis. Further investigation indicated that the IGF2BP3/glutathione peroxidase 4 (GPX4) axis was involved in mollugin-regulated ferroptosis in CRC. In conclusions, Mollugin suppresses proliferation and drives ferroptosis of CRC cells by inhibiting the IGF2BP3/GPX4 axis, suggesting that mollugin may be a potential therapeutic option for CRC.

Circ_0014130 is involved in the drug sensitivity of colorectal cancer through miR-197-3p/PFKFB3 axis.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the most deadly cancers in the world, with few treatments and a poor prognosis. In recent years, many circular RNAs have been studied in CRC, but the role of circ_0014130 in CRC has not been investigated. Therefore, this research is designed to investigate the impact of circ_0014130 on the resistance of 5-fluorouracil (5-FU) in CRC. METHODS: Quantitative real-time polymerase chain reaction was conducted to assess the expression of circ_0014130, microRNA-197-3p (miR-197-3p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3). The expression of PFKFB3 protein was detected by Western blot. The effect of cric_0014130 on drug resistance in CRC was verified by Cell Counting Kit-8 assay, clone formation assay, Transwell, and flow cytometry. The effect of circ_0014130 on tumor growth was evaluated by xenograft tumor model in vivo. RESULTS: Circ_0014130 and PFKFB3 were increased, while miR-197-3p was reversed in CRC tissues and cells. Knocking down circ_0014130 can promote cell apoptosis, inhibit the proliferation of CRC cells, and reduced the IC50 of 5-FU. In addition, miR-197-3p inhibitors reversed the effect of si-circ_0014130 on CRC cells. Similarly, overexpression of PFKFB3 can regulate CRC cell behavior and 5-FU resistance caused by miR-197-3p. Finally, decrease of circ_0014130 was demonstrated to enhance the resistance of 5-FU in CRC tissues in vivo. CONCLUSION: Circ_0014130 modulates 5-FU resistance in CRC by modulating the miR-197-3p/PFKFB3 axis, which is helpful for drug chemotherapy in CRC.

Efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.

BACKGROUND: At present, colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively. The adverse effects (AEs) of chemotherapy usually interrupt the treatment of chemotherapy. Traditional Chinese medicine (TCM) has demonstrated great potential in improving patients' clinical symptoms, regulating the immune function, improving the life quality, and reducing the AEs of chemotherapy. AIM: To observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation. METHODS: Data from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group. The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen, while the control group was given the CAPOX regimen alone. After six cycles of chemotherapy, the scores of TCM symptoms, Karnofsky performance scale (KPS) score, levels of T-cell subsets, and AEs after chemotherapy of the two groups were compared. RESULTS: A total of 70 patients were randomly divided into either an experimental group (n = 35, no dropout) or a control group (n = 33, with 2 dropouts). Compared with the control group, the experimental group improved significantly (P < 0.05) in scores of TCM symptoms, KPS score, levels of T-cell subsets, and AEs of chemotherapy. CONCLUSION: Yiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency, regulate the immune function, and alleviate the AEs of chemotherapy, so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.

Effect of miRNA-136-targeted regulation of FGFR1 on proliferation and apoptosis of triple-negative breast cancer cells.

PURPOSE: This study was designed to investigate the effect of micro RNA-targeted regulation of FGFR1 on the proliferation and apoptosis of triple-negative breast cancer (TNBC) cells. METHODS: TNBC (MAD-MB-231), three types of breast cancer (MCF10A, MCF7, ZR751) cell lines, and normal breast tissue cell lines were extracted. Real-time PCR was used to detect the expression of miRNA-136 in different types of breast cells. The MAD-MB-231 cell lines were transfected with miRNA-136 mimic by lipofection. The effects of miRNA-136 on FGFR1 expression and apoptosis rate of MAD-MB-231 cell lines were determined using western blotting. RESULTS: miRNA-136 expression in TNBC cells was lower than that of controls, and was negatively correlated with TNM staging. miRNA-136 expression in MCF10A, MCF7, ZR751, and MAD-MB-231 cell lines was gradually decreased, and MCF10A expression in the other three cell lines was significantly higher than that of MAD-MB-231 cell line (P<0.05). Transfection with miRNA-136 significantly reduced the proliferation rate of MAD-MB-231, and a higher concentration and longer duration exhibited a more pronounced inhibitory effect on proliferation (P<0.05). Transfection with miRNA-136 significantly reduced FGFR1 expression in the MAD-MB-231 cell lines, without significantly affecting apoptosis. CONCLUSION: miRNA-136 shows a very low expression level in TNBC cells. Transfection with miRNA-136 can significantly inhibit the proliferation of TNBC cells by external transfection, and has little effect on cell apoptosis. This may be related to miRNA-mediated changes in FGFR1 protein expression.

Wnt/ß-catenin signaling plays a key role in the development of spondyloarthritis.

Spondyloarthritis (SpA) is a group of diseases consisting of psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel disease (a subgroup of juvenile idiopathic arthritis), and ankylosing spondylitis (the prototype of SpA). Axial bone formation and the combination of concurrent erosion and new bone formation are specific characteristics of SpA disease. The use of antiproinflammatory cytokines, such as inhibitors of tumor necrosis factor α (TNF-α), appears to be the greatest advance in the treatment of SpA over the past 20 years. However, TNF-α blockers do not halt new bone formation. Recent clinical observations and animal studies demonstrate that Wnt signaling proteins and natural Wnt inhibitors, such as DKK1 and sclerostin, are likely to play important roles in the process of ankylosis in SpA, and could potentially serve as therapeutic targets for the treatment of SpA.

Effects of Feijining Decoction on vascular endothelial growth factor protein expression and changes of T cell subsets in Lewis lung carcinoma-bearing mice.

Angiogenesis is crucial for cancer growth and metastasis. T cells are also key members of the adaptive immunity against tumorigenesis. The aim of the present study was to observe the effects of Feijining Decoction (FJND) on vascular endothelial growth factor (VEGF) protein expression and T cell subsets [cluster of differentiation 4+(CD4+) and CD8+ T lymphocyte] in Lewis lung carcinoma (LLC)-bearing mice. C57BL/6J mice were subcutaneously implanted with LLC cells. Forty carcinoma-bearing mice were randomly assigned to four groups (10 animals/group). The control group (CG) were the untreated group, the cisplatinum (DDP) group (DG) mice were treated with DDP, the FJND group (FG) were treated with FJND and the FJND + DDP group (FDG) were treated with FJND and DDP. Western blot and flow cytometry were used to evaluate the VEGF protein expression of tumor tissue and T cell subsets of the spleen. Spontaneous activity in 5 min was observed by the photoelectric counting method. DDP + FJND (FDG group) markedly inhibited tumor growth compared to the DG mice. The protein expression of VEGF was significantly downregulated in the carcinoma of FG mice compared to CG mice. VEGF protein expression was significantly reduced in FDG compared to DG mice. In the FG mice, the splenic CD4+ and CD4+/CD8+ cells were significantly increased compared to the CG mice, and the splenic CD4+ cells in the FDG mice were significantly increased compared to the DG group. In conclusion, FJND can inhibit tumor growth by downregulating VEGF protein expression and improving the immune function.

[Effects of biological regulated measures on active organic carbon and erosion-resistance in the Three Gorges Reservoir region soil].

To gain a better knowledge of characteristics of soils and provide a scientific basis for soil erosion control in the Three Gorges Reservoir Area, contents of aggregates and total soil organic carbon (SOC), as well as soil active organic carbon fractions including particulate organic carbon (POC), readily oxidized organic carbon (ROC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) in the 0-30 cm soil layer under seven different biological regulated measures were studied by the field investigation combined with the laboratory analysis. Results showed that the content of the SOC and active organic carbon fractions decreased with the increasing soil depth; the content of the SOC and active organic carbon fractions in 0-10 cm was significantly higher than that in 20-30 cm. The stability of soil aggregates were also significantly influenced by biological regulated measures, the content of > 0.25 mm water-stable aggregates in seven types of biological regulated measures was in the order of Koelreuteria bipinnata + Cassia suffruticasa > hedgerows > closed forest > natural restoration > economic forest > traditional planting > control plot, moreover, the content of 0.25 mm water-stable aggregates correlated positively with the content of SOC. Soils under different biological regulated measures all demonstrated fractal features, and soil under the measure of Koelreuteria bipinnata + Cassia suffruticasa was found to have the lowest value of fractal dimension and soil erodiable K, indicating a relatively strong structure stability and erosion-resistant capacity. Negative correlation was observed when compared the content of active organic carbon fractions with the soil erodiable K. It can be concluded that properties of soil can be managed through biological regulated measures; thence had an influence on the soil erosion-resistant capacity.

[Design, synthesis and PPAR agonist activities of novel L-tyrosine derivatives containing phenoxyacetyl moiety].

The design, synthesis and bioevaluation of a series of novel L-tyrosine derivatives as peroxisome proliferator-activated receptor (PPAR) agonists are reported. Four intermediates and twenty L-tyrosine derivatives containing phenoxyacetyl moiety TM1 were synthesized starting from L-tyrosine via four step reactions including the esterification of carboxyl group, phenoxyacetylation of a-amino group, bromoalkylation of phenolic hydroxyl group and then nucleophilic substitution reaction with various heterocyclic amines in 21%-75% overall yield. Subsequently TM1 were hydrolyzed to give sixteen corresponding target compounds TM2 in 77%-99% yield. The chemical structures of the thirty-nine new compounds were identified using 1H NMR, 13C NMR techniques and thirty-five were confirmed by HR-MS techniques. Screening results in vitro showed that the PPAR relative activation activities of the target molecules are weak overall, while compound TM2i reaches 50.01%, which hints that the molecular structures of these obtained compounds need to be modified further.