CXCL1/IGHG1 signaling enhances crosstalk between tumor cells and tumor-associated macrophages to promote MC-LR-induced colorectal cancer progression.

Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.

First Survey of the Pathogenic Fungus Batrachochytrium dendrobatidis in Wild Populations of the Yunnan Caecilian (Ichthyophis bannanicus) in Guangxi, China.

Batrachochytrium dendrobatidis (Bd), which causes chytridiomycosis, mainly infects Anura and Caudata but is poorly known in Gymnophiona. We conducted a survey of Bd in the Yunnan caecilian (Ichthyophis bannanicus) and found that 6 of 71 samples (8.4%) tested positive for Bd. To our knowledge, this is the first detection of Bd in wild I. bannanicus.

Elevated Krüppel-like factor 5 expression in spatiotemporal mouse lungs is similar to human congenital cystic adenomatoid malformation of the lungs.

Objective The study aimed to investigate the role of high Krüppel-like factor 5 (KLF5) expression on the pathogenesis of congenital cystic adenomatoid malformation of the lungs (CCAML) in mice. Methods A mouse model of high KLF5 expression in the lungs was established. KLF5 expression and the pulmonary lumen diameter were examined by immunohistochemistry to determine a successful model. Basement membrane damage and activity of matrix metalloproteinase-9 (MMP-9) were examined. After an adenovirus carrying KLF5 gene transfection in lung adenocarcinoma (H441) was created, changes in expression and activity of MMP-9 were determined. Results In a mouse model with high KLF5 expression, the pulmonary lumen was markedly enlarged, indicating establishment of CCAML. The basement membrane was degraded, and MMP-9 activity was significantly higher in the model group compared with the control group. Moreover, mice in a cellular model after transfection also showed higher MMP-9 activity than did controls. Conclusion High KLF5 expression may play a pivotal role in the pathogenesis of CCAML, partly through regulating the activity of MMP-9.

High-level expression and purification of human epidermal growth factor with SUMO fusion in Escherichia coli.

Human epidermal growth factor (hEGF) can stimulate the division of various cell types and has potential clinical applications. However, the high expression of active hEGF in Escherichia coli has not been successful, as the protein contains three intra-molecular disulfide bonds that are difficult to form correctly in the bacterial intracellular environment. To solve this problem, we fused the hEGF gene with a small ubiquitin-related modifier gene (SUMO) by synthesizing an artificial SUMO-hEGF fusion gene that was highly expressed in Origami (DE3) strain. The optimal expression level of the soluble fusion protein, SUMO-hEGF, was up to 38.9% of the total cellular protein. The fusion protein was purified by Ni-NTA affinity chromatography and cleaved by a SUMO-specific protease to obtain the native hEGF, which was further purified by Ni-NTA affinity chromatography. The result of the reverse-phase HPLC showed that the purity of the recombinant cleaved hEGF was greater than 98%. The primary structure of the purified hEGF was confirmed by N-terminal amino acid sequencing and MALDI-TOF mass spectroscopy analysis. Using the method of methylthiazoletetrazolium, the mitogenic activity on Balb/c 3T3 cells of the purified hEGF was comparable to that of commercial hEGF.

A comparison of anesthetic regimens using etomidate and propofol in patients undergoing first-trimester abortions: double-blind, randomized clinical trial of safety and efficacy.

BACKGROUND: This prospective study compared the safety, recovery time and side effects of six distinct general anesthesia regimens for first-trimester surgical abortion. STUDY DESIGN: Two hundred forty women scheduled for surgical abortion at 6 to 8 weeks of gestation were randomized into three groups (n=40) of propofol: group P (2 mg/kg propofol alone), group PF (2 mg/kg propofol+1 mcg/kg fentanyl), group PMF (2 mg/kg propofol+1 mcg/kg fentanyl+0.02 mg/kg midazolam) and three groups (n=40) of etomidate: group E (0.2 mg/kg etomidate alone), group EF (0.2 mg/kg etomidate+1 mcg/kg fentanyl) and group EMF (0.2 mg/kg etomidate+1 mcg/kg fentanyl+0.02 mg/kg midazolam). Vital signs including pulse oxygen saturation (SpO2), mean arterial pressure (MAP) and heart rate were recorded as the primary outcomes. The recovery time and side effects were recorded as secondary outcomes. RESULTS: During induction, SpO2 and MAP decreased significantly in all the three groups of propofol and were significantly lower than those in the groups of etomidate. Mean recovery times to both eye opening and to obeying commands were significantly shorter in group PF than those in groups P and PMF, while there were no significant differences among the three groups of etomidate. Compared with the etomidate groups, the incidence of injection-induced pain was significantly higher, while the scores of myoclonus and postoperative nausea and vomiting were lower, in the three propofol groups. Moreover, myoclonus scores as well as nausea and vomiting scores were lower in group EMF than in groups E and EF. CONCLUSIONS: The results of this study suggest that (a) etomidate is much safer than propofol for first-trimester surgical abortions and (b) using a lower dose of etomidate, supplemented with fentanyl and midazolam, is more beneficial than the use of etomidate with or without fentanyl in reducing adverse effects like myoclonus and postoperative nausea and vomiting.