Vitexicarpin suppresses malignant progression of colorectal cancer through affecting c-Myc ubiquitination by targeting IMPDH2.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and is characterised by extensive invasive and metastatic potential. Previous studies have shown that vitexicarpin extracted from the fruits of Vitex rotundifolia can impede tumour progression. However, the molecular mechanisms involved in CRC treatment are still not fully established. PURPOSE: Our study aimed to investigate the anticancer activity, targets, and molecular mechanisms of vitexicarpin in CRC hoping to provide novel therapies for patients with CRC. STUDY DESIGN/METHODS: The impact of vitexicarpin on CRC was assessed through various experiments including MTT, clone formation, EDU, cell cycle, and apoptosis assays, as well as a tumour xenograft model. CETSA, label-free quantitative proteomics, and Biacore were used to identify the vitexicarpin targets. WB, Co-IP, Ubiquitination assay, IF, molecular docking, MST, and cell transfection were used to investigate the mechanism of action of vitexicarpin in CRC cells. Furthermore, we analysed the expression patterns and correlation of target proteins in TCGA and GEPIA datasets and clinical samples. Finally, wound healing, Transwell, tail vein injection model, and tissue section staining were used to demonstrate the antimetastatic effect of vitexicarpin on CRC in vitro and in vivo. RESULTS: Our findings demonstrated that vitexicarpin exhibits anticancer activity by directly binding to inosine monophosphate dehydrogenase 2 (IMPDH2) and that it promotes c-Myc ubiquitination by disrupting the interaction between IMPDH2 and c-Myc, leading to epithelial-mesenchymal transition (EMT) inhibition. Vitexicarpin hinders the migration and invasion of CRC cells by reversing EMT both in vitro and in vivo. Additionally, these results were validated by the overexpression and knockdown of IMPDH2 in CRC cells. CONCLUSION: These results demonstrated that vitexicarpin regulates the interaction between IMPDH2 and c-Myc to inhibit CRC proliferation and metastasis both in vitro and in vivo. These discoveries introduce potential molecular targets for CRC treatment and shed light on new mechanisms for c-Myc regulation in tumours.

CT and MR imaging features of soft tissue rhabdoid tumor: compared with rhabdomyosarcoma in children.

Objective: To assess the computed tomography (CT) and magnetic resonance (MR) imaging characteristics of soft tissue rhabdoid tumors (RT) and compare them with those of rhabdomyosarcoma (RMS). Methods: We conducted a retrospective analysis of 49 pediatric patients from 2011 to 2022, comprising 16 patients with soft tissue RT and 33 patients with RMS who underwent CT or MRI scans. Key imaging features, as well as clinical and pathological data, were compared between the two groups. The multivariate logistic regression analysis was used to determine independent differential factors for distinguishing soft tissue RT from RMS, and the model was established. The final prediction model was visualized by nomograms and verified internally by using a bootstrapped resample 1,000 times. The diagnostic accuracy of the combined model was assessed in terms of discrimination, calibration, and clinical utility. Results: Age, sex, number of lesions, and primary locations were similar in both groups. The imaging characteristics, including margin, calcification, surrounding blood vessels, and rim enhancement, were associated with the two groups of soft tissue tumors, as determined by univariate analysis (all p < 0.05). On multivariate logistic regression analysis, the presence of unclear margin (p-value, adjusted odds ratio [95% confidence interval]: 0.03, 7.96 [1.23, 51.67]) and calcification (0.012, 30.37 [2.09, 440.70]) were independent differential factors for predicting soft tissue RT over RMS. The presence of rim enhancement (0.007, 0.05 [0.01, 0.43]) was an independent differential factor for predicting RMS over soft tissue RT. The comprehensive model established by logistic regression analysis showed an AUC of 0.872 with 81.8% specificity and 81.3% sensitivity. The decision curve analysis (DCA) curve displayed that the model achieved a better net clinical benefit. Conclusion: Our study revealed that the image features of calcification, indistinct margins, and a lack of rim enhancement on CT and MRI might be reliable to distinguish soft tissue RT from RMS.

The mind-tranquilizing and menstruation-regulating method for acupuncture treatment of delayed menstrual cycle--a clinical controlled study.

OBJECTIVE: To compare the therapeutic effects of the mind-tranquilizing and menstruation-regulating acupuncture method with the routine acupuncture method in treating delayed menstrual cycle. METHODS: 40 patients with delayed menstrual cycle were randomly divided into a treatment group of 23 cases (treated by the mind-tranquilizing and menstruation-regulating acupuncture method), and a control group of 17 cases (treated by the routine acupuncture method for delayed menstrual cycle due to stagnation of the liver-qi). The treatment involved three menstrual cycles. The evaluations were done by scoring the symptoms before treatment and at the end of each menstrual cycle. RESULTS: After treatment, significant differences were found between the two groups in the therapeutic effects (P<0.05). CONCLUSION: The therapeutic effect of the mind-tranquilizing and menstruation-regulating acupuncture method is significantly superior to that of the routine acupuncture method for delayed menstrual cycle.

[Alleles of HLA class II DRB1 of patients with essential hypertension in Yunnan Hans].

OBJECTIVE: To investigate the association between the alleles of human leukocyte antigens (HLA)-DRB1 and essential hypertension (EH) in the Hans living in Yunnan of China. METHODS: The alleles of HLA-DRB1 were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in samples from 83 patients with essential hypertension and 91 healthy controls. All of the subjects, their grandparents and grand-grandparents are Hans living in Yunnan of China. RESULTS: The frequency of DRB1*1501/2 in the EH patients (0.219) was significantly higher than that in the controls(0.060), chi quare=18.331, P<0.01. Relative risk (RR) was 4.46, and etiologic factor (EF) was 0.34. The frequency of DRB1*0901 significantly decreased in the group of patients with EH in comparison to the controls (0.081 versus 0.192) chi-square=8.704 P<0.05. RR was 0.41 and prevention factor(PF) was 0.19. CONCLUSION: HLA-DRB1*1501/2 is associated with the susceptibility to essential hypertension in the Yunnan Hans of China. DRB1*0901 may protect one from the disease.