Clinical Significance and Oncogenic Activity of GRWD1 Overexpression in the Development of Colon Carcinoma.

OBJECTIVE: GRWD1 (glutamate-rich WD40 repeat containing 1) is a multifunctional protein involved in multiple cellular regulatory pathways, particularly those associated with cell growth control. GRWD1 is represented as a potential oncogene in several cancers, however, the function and mechanism of GRWD1 in the development of colon cancer are still unknown. MATERIALS AND METHODS: IHC was used to detect the expression of GRWD1 in colon carcinoma tissues. CCK-8, colony formation, and EdU were used to measure the cell proliferation after GRWD1 knockdown and overexpression. The distribution of the cell cycle was analyzed by flow cytometry. The effect of GRWD1 knockdown on migration and invasion was analyzed by wound healing and transwell assays. RESULTS: Overexpression of GRWD1 in colon carcinoma tissues was associated with pathological grading, tumor size, N stage, TNM stage, and poor survival. GRWD1 had high sensitivity and specificity in distinguishing colon cancer from noncancerous tissues, and might be served as an independent prognosis in colon carcinoma patients. Knockdown of GRWD1 significantly inhibited the cell proliferation and colony formation, and induced cell cycle arrest and more drug susceptibility, and suppressed the migration and invasion. GRWD1 exhibited these oncogenic activities might be associated with its regulation on the expression of PCNA and Ki67, Cyclin A2 and Cyclin B1, ABCC1 and GSTP1, MTA1 and MTA2. CONCLUSION: GRWD1 may play an oncogenic activity in the development of colon carcinoma and its overexpression was associated with malignant characteristics and poor survival outcome of colon carcinoma. GRWD1 might be a potential target for future therapy.

Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer.

Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan-Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P<0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P<0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.

Mapping the Galvanic Corrosion of Three Metals Coupled with a Wire Beam Electrode: The Influence of Temperature and Relative Geometrical Position.

The local electrochemical properties of galvanic corrosion for three coupled metals in a desalination plant were investigated with three wire-beam electrodes as wire sensors: aluminum brass (HAl77-2), titanium (TA2), and 316L stainless steel (316L SS). These electrodes were used with artificial seawater at different temperatures. The potential and current-density distributions of the three-metal coupled system are inhomogeneous. The HAl77-2 wire anodes were corroded in the three-metal coupled system. The TA2 wires acted as cathodes and were protected; the 316L SS wires acted as secondary cathodes. The temperature and electrode arrangement have important effects on the galvanic corrosion of the three-metal coupled system. The corrosion current of the HAl77-2 increased with temperature indicating enhanced anode corrosion at higher temperature. In addition, the corrosion of HAl77-2 was more significant when the HAl77-2 wires were located in the middle of the coupled system than with the other two metal arrangement styles.

Biflavone Ginkgetin, a Novel Wnt Inhibitor, Suppresses the Growth of Medulloblastoma.

Medulloblastoma (MB) is a form of malignant brain tumor that predominantly arises in infants and children, of which approximately 25 % is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1. Therefore, Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer. In our present study, we undertook a screening for antagonists of Wnt signaling from 600 natural compounds, and identified Ginkgetin, a biflavone isolated from Cephalotaxus fortunei var. alpina. Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 µM and structure-activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group. Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells. Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells. Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes, including Axin2, cyclinD1 and survivin in MB cells. The phosphorylation level of ß-catenin also decreased in a time- and concentration-dependent manner. Collectively, our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling, and as such warrants further exploration as a promising anti-medulloblastoma candidate.

One-step semisynthesis method of spirocurcasone and pyracurcasone from curcusones A and B.

High contents of curcusones A and B and trace amounts of spirocurcasone exist in the roots of Jatropha curcas. Here, a one-step semisynthesis method of spirocurcasone and pyracurcasone was built, not only resulted an increased yield of spirocurcasone but also produced pyracurcasone, which exhibited greater cytotoxicity compared to curcusones A and B. The plausible mechanism of the formation of pyracurcasone was proposed, and the proposed biogenetic origin for spirocurcasone by Taglialatela-Scafati was confirmed.

Cytotoxicity of naturally occurring rhamnofolane diterpenes from Jatropha curcas.

Twelve rhamnofolane diterpenoids, including curcusecons A-E with unusual seco-rhamnofolane skeletons, curcusones F-J, 4-epi-curcusone E, and 3-dehydroxy-2-epi-caniojane, together with seven known analogues, curcusones A-E, jatrogrossidione, and 2-epi-jatrogrossidione, were isolated from the roots of Jatropha curcas. Their structures were determined by extensive spectroscopic methods, and the relative stereochemistry of curcusecon B was further confirmed by X-ray crystallographic data. Their cytotoxity against five human cancer cells was studied and the results indicated that the dienone system in ring B was essential for cytotoxicity of these compounds.

New eudesmenoic acid methyl esters from the seed oil of Jatropha curcas.

Three new eudesmenoic acid methyl esters (1-3), as well as five known compounds, including three germacranolides (4-6) and two eudesmanolides (7 and 8), were isolated from the seed oil of Jatropha curcas. The new compounds were elucidated by means of spectroscopic methods, including extensive NMR spectra. In addition, the structure of 8 was confirmed by a single-crystal X-ray diffraction analysis. Among the isolates, compounds 4-6 were the first reported from the genus Jatropha. Using MTS viability assay, the cytotoxicity of compounds 2-8 were evaluated against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines. Compounds 4 and 5 showed remarkable cytotoxicity against all the tested cell lines with IC50 values from 0.5 to 3.5 µM, and the new compound 3 displayed selective cytotoxic activity against A-549 cell with an IC50 value of 7.24 µM, but slight cytotoxicity against HL-60 and MCF-7 with IC50 values of 23.77 and 22.37 µM, respectively.

Multidisciplinary intensive care in extensive necrotizing fasciitis.

This is a case report of extensive necrotizing fasciitis (NF). A 65-year-old man presented with high fever, pain, swelling, and redness of the perineum, scrotum, and right lower limb. Based on the clinical symptoms and an imaging examination, a diagnosis of NF was made. The patient underwent an extensive exploration followed by daily bedside debridement. A diversion colostomy and six additional debridement procedures on the right thigh and perineum were subsequently performed. Although the patient had an eventful course, he recovered well under a multidisciplinary treatment regimen. The treatment and hospital course of the patient are described.

[An experimental study on high intensity focused ultrasound combined with mitomycin treatment of bladder tumor].

OBJECTIVE: To study the therapeutic effect and synergistic inhibition effect of high intensity focused ultrasound in combination with mitomycin on T739 mice bladder tumor. METHODS: BTT739 tumor-bearing mice receiving HIFU and/or mitomycin in two weeks, were divided into control group, low dose chemotherapy group, high dose chemotherapy group, HIFU group and HIFU combined chemotherapy group. The growth of mice tumor volume was observed in two weeks, by which we counted tumor volume doubling time and performed the growth curve. All specimens were analysed histologically. RESULTS: HIFU combined mitomycin has significant synergistic inhibition effect. Tumor tissue damage such as huge coagulation necrosis was observed using light microscopy. However, there were still some remaining alive cells. The apoptosis of tumor cell in HIFU group and HIFU combined chemotherapy group obviously increased in comparison with other groups. CONCLUSIONS: HIFU group, HIFU combined chemotherapy group can distinctively inhibit tumor growth; HIFU combined with mitomycin has notable synergistic inhibitory effect. HIFU may induce the apoptosis of tumor cell.