Cisatracurium regulates the CXCR4/let-7a-5p axis to inhibit colorectal cancer progression by suppressing TGF-ß/SMAD2/3 signalling.

OBJECTIVE: To reveal the effects and related mechanism of cisatracurium on colorectal cancer (CRC) development. METHODS: HCT116 and SW480 cells were treated with various concentrations of cisatracurium or transforming growth factor-ß (TGF-ß). Chemokine C-X-C-Motif Receptor 4 (CXCR4) was overexpressed and let-7a-5p was silenced in cells by transfection with pcDNA3.1-CXCR4 or let-7a-5p inhibitor. Cell Counting Kit-8 (CCK-8) assay measured cell viability, and transwell and wound healing assays evaluated cell invasion and migration, respectively. The expression levels of let-7a-5p and CXCR4 were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was conducted to test the levels of CXCR4, TGF-ß/SMAD2/3 signalling and metastasis-related proteins. A tumour xenograft assay was performed to assess tumour growth. RESULTS: Cisatracurium treatment suppressed the viability and metastasis of HCT116 and SW480 cells in a concentration-dependent manner, whereas activating TGF-ß/SMAD2/3 signalling significantly reversed these effects. Cisatracurium treatment markedly reduced CXCR4 expression by inhibiting TGF-ß/SMAD2/3 signalling. Besides, let-7a-5p was identified as a target of CXCR4 and could be upregulated by cisatracurium. Both CXCR4 overexpression and let-7a-5p knockdown alleviated the biological roles of cisatracurium in CRC cells. Moreover, a tumour xenograft assay further confirmed that cisatracurium inhibited tumour growth and metastasis by increasing let-7a-5p expression. CONCLUSION: Cisatracurium suppressed the viability, metastasis and tumour growth of CRC by regulating the CXCR4/let-7a-5p axis via inhibiting TGF-ß/SMAD2/3 signalling. These findings provide a theoretical basis for the role of cisatracurium in the prognosis of CRC patients.

Butyrate Improves the Metabolic Disorder and Gut Microbiome Dysbiosis in Mice Induced by a High-Fat Diet.

Background: Metabolic syndrome (MS) is one of the major causes of coronary artery diseases (CAD). Gut microbiome diversity and its natural fermentation products are not only correlated with MS and CAD, but their correlations also appear to be stronger than the associations with traditional risk factors. Therefore, the aim of this study was to provide a new potential pathway for the natural fermentation product butyrate to improve MS and to examine whether it is associated with serum metabolic profiles and gut flora composition. Methods: C57BL/6J mice fed a high-fat diet (HFD) were treated with 400 mg/kg of sodium butyrate for 16 weeks. Blood and fecal samples were collected, and the metabolite concentrations and 16s rRNA were measured with liquid chromatography-MS and Illumina platform, respectively. The plasma differential metabolites and gut microbiome composition were analyzed with XCMS online and QIIME 2, respectively. Results: Gut microbiome-derived butyrate reduced glucose intolerance and insulin resistance, resisting HFD-induced increase in the relative abundance of f_Lachnospiraceae, f_Rikenellaceae, and f_Paraprevotellaceae. Meanwhile, sodium butyrate increased the levels of α-linolenate, all-trans-retinal, resolvin E1, and leukotriene in the plasma, and the differential pathways showed enrichment in mainly resolvin E biosynthesis, histidine degradation, lipoxin biosynthesis, and leukotriene biosynthesis. Moreover, sodium butyrate increased the levels of phosphorylated-adenosine 5'-monophosphate-activated protein kinase (p-AMPK) and facilitated glucose transporter member 4 (GLUT4) in the adipose tissue. Conclusion: Butyrate can induce AMPK activation and GLUT4 expression in the adipose tissue, improving cardiovascular disease (CVD)-related metabolic disorder, resisting HFD-induced gut microbiome dysbiosis, and promoting resolvin E1 and lipoxin biosynthesis. Oral supplement of the natural fermentation product butyrate can be a potential strategy for preventing CVD.

Facile synthesis of S-Ag nanocomposites and Ag2S short nanorods by the interaction of sulfur with AgNO3 in PEG400.

A facile, eco-friendly and inexpensive method to prepare Ag2S short nanorods and S-Ag nanocomposites using sublimed sulfur, AgNO3, PVP and PEG400 was studied. According to x-ray diffraction and scanning electron microscopy of the Ag2S, the products are highly crystalline and pure Ag2S nanorods with diameters of 70-160 nm and lengths of 200-360 nm. X-ray diffraction of the S-Ag nanocomposites shows that we obtained cubic Ag and S nanoparticles. Transmission electron microscopy shows that the molar ratio of PVP to Ag(+) plays an important role in controlling the size and morphology of the S-Ag nanocomposites. When the molar ratio of PVP to Ag(+) was 10:1, smaller sizes, better dispersibility and narrower distribution of S-Ag nanocomposites with diameters of 10-40 nm were obtained. The formation mechanism of the S-Ag nanocomposites was studied by designing a series of experiments using ultraviolet-visible measurement, and it was found that S nanoparticles are produced first and act as seed crystals; then Ag(+) becomes Ag nanocrystals on the surfaces of the S nanoparticles by the reduction of PVP. PEG400 acts as a catalyzer, accelerating the reaction rate, and protects the S-Ag nanocomposites from reacting to produce Ag2S. The antimicrobial experiments show that the S-Ag nanocomposites have greater antimicrobial activity on Staphylococcus aureus, Aspergillus niger and blue mold than Ag nanoparticles.

[NIR spectroscopy combined with stability and equivalence MW-PLS method applied to analysis of hyperlipidemia indexes].

UNLABELLED: Moving window partial least square (MW-PLS) method was improved by considering the stability and equivalence, and was used for the wavelength optimization of reagent-free near-infrared (NIR) spectroscopic analysis of total cholesterol (TC) and triglycerides (TG) for hyperlipidemia. A random and stability-dependent framework of calibration, prediction, and validation was proposed. From all human serum samples (negative 145 and positive 158, a total of 303 sample), 103 samples (negative 44 and positive 59) were randomly selected for the validation set, the remaining samples (negative 101 and positive 99, a total of 200 sample) were used as modeling set; then the modeling set was randomly divided into calibration set (negative 51 and positive 49, a total of 100 sample) and prediction set (negative 50 and positive 50, a total of 100 sample) by 50 times. To produce modeling stability, the model parameters were optimized based on the average prediction effect for all divisions; the optimized models were validated by using the validation samples. The obtained optimal MW-PLS wavebands were 1,556~1,852 nm for TC and 1,542-1,866 nm for TG. In order to solve the problem that instrument design typically involves some limitations of position and number of wavelengths because of cost and material properties, the equivalent model sets were proposed, and a unique public waveband 1,542-1,852 nm of the equivalent model sets for TC, TG was found. The validation results show that: using the optimal MW-PLS wavebands, validation samples' root mean square error of prediction (V SEP) for TC, TG were 0.177, 0.100 mmol · L(-1), the correlation coefficient of prediction (V_Rp) for TC, TG were 0.988, 0.996, and the sensitivity and specificity for hyperlipidemia achieved 95.0%, 90.5%, respectively; using the public equivalent wavebands, the V_SEP for TC, TG were 0.177, 0.101 mmol · L(-1)), the V_Rp for TC, TG were 0.988, 0.996, and the sensitivity and specificity achieved 92.7%, 90.3%, respectively. CONCLUSION: NIR spectroscopy combined with the stability and equivalenceimprovement MW-PLS method can provide a potential tool for detecting hyperlipidemia for large population.