murine-appendectomy-model-chronic-colitis-associated-colorectal

Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch

The human appendix has been recently implicated to play important biological roles in the pathogenesis of various complex diseases, such as colorectal ...

xi'an jiaotong university

University of Health Network

The use of chicken blastodermal cells (CBC) in the production of transgenic chickens requires incorporation of the desired stable genetic modification into CBC. With greater proportions of stably transfected blastodermal cells in the embryo inoculum, the frequency of intermediate chimeric birds is greater. Magnetic-activated cell sorting (MACS) was evaluated as a method for enrichment of transfected CBC. This approach requires surface expression of a molecule that can be recognized by an antibody. Chicken blastodermal cells from fertilized Barred Plymouth Rock eggs were coelectroporated with pmiwZ and pMACS Kk and were sorted magnetically by expression of the mouse H-2Kk molecule on the surface of successfully transfected cells. The effectiveness of sorting was assessed using X-gal staining to detect lacZ expression from the pmiwZ plasmid. After 48 h of culture, lacZ-positive cells appeared to be enriched 1.4-fold in the MACS selected population. Cells from this enriched pool contributed to extra-embryonic and intra-embryonic tissues of 72-h White Leghorn recipient embryos with a marginal increase in levels of intra-embryonic contribution. Our demonstration that transfected, cultured, and magnetically sorted CBC maintain their ability to contribute to ectodermal and mesodermal lineages of intra-embryonic tissues illustrates the potential value of this technique for introducing genetic modifications into birds.

Selection of genetically modified chicken blastodermal cells by magnetic-activated cell sorting.

Enchondroma and chondrosarcoma are the most common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. We performed RNA-seq analysis on chondrocytes from Col2a1Cre;Idh1LSL/+ animals and found that genes implied in cholesterol synthesis pathway were significantly upregulated in the mutant chondrocytes. We examined the phenotypic effect of inhibiting intracellular cholesterol biosynthesis on enchondroma formation by conditionally deleting SCAP (sterol regulatory element-binding protein cleavage-activating protein), a protein activating intracellular cholesterol synthesis, in IDH1 mutant mice. We found fewer enchondromas in animals lacking SCAP. Furthermore, in chondrosarcomas, pharmacological inhibition of intracellular cholesterol synthesis significantly reduced chondrosarcoma cell viability in vitro and suppressed tumor growth in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.

Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.

Oral supplemented nutraceuticals derived from food sources are surmised to improve the human health through interaction with the gastrointestinal bacteria. However, the lack of fundamental quality control and authoritative consensus (e.g., formulation, route of administration, dose, and dosage regimen) of these non-medical yet bioactive compounds are one of the main practical issues resulting in inconsistent individual responsiveness and confounded clinical outcomes of consuming nutraceuticals. Herein, we studied the dose effects of widely used food supplement, microalgae  (), on the colonic microbiota and physiological responses in healthy male  mice. Based on the analysis of 16s rDNA sequencing, compared to the saline-treated group, oral administration of  once daily for 24 consecutive days altered the diversity, structure, and composition of colonic microbial community at the genus level. More importantly, the abundance of microbial taxa was markedly differentiated at the low (1.5 g/kg) and high (3.0 g/kg) dose of , among which the relative abundance of , and  were modulated at various degrees. Evaluation of serum biomarkers in mice at the end of  intervention showed reduced the oxidative stress and the blood lipid levels and increased the level of appetite controlling hormone leptin in a dose-response manner, which exhibited the significant correlation with differentially abundant microbiota taxa in the cecum. These findings provide direct evidences of dose-related modulation of gut microbiota and physiological states by , engendering its future mechanistic investigation of  as potential sources of prebiotics for beneficial health effects  the interaction with gut microbiota.

Qingxia Wei

Department of General Surgery,
The First Affiliated Hospital,
Department of General Surgery, The First Affiliated Hospital

xi'an jiaotong university

Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch

Qingxia Wei

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of General Surgery,The First Affiliated Hospital,Department of General Surgery, The First Affiliated Hospital

xi'an jiaotong university

Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch

Department of General Surgery,
The First Affiliated Hospital,
Department of General Surgery, The First Affiliated Hospital