AIM: To discuss the establishment of immediate diabetic keratopathy animal model of C57BL/6 mouse induced by ahigh-fat and high-glucose diet.
METHODS: Diabetes mellitus was induced by a high-fat and high-glucose diet in C57BL/6 mouse. 1% rose bengal was stained on the cornea to examine the integrality of the corneal epithelium at 2 ~ 12mo after completion of the model. Corneal epithelial wound healing was observed using a vivo epithelial debridement model which was dyed by sodium fluorescein. Corneal morphology histology was examined by pathological methods.
RESULTS: The high-fat and high-glucose diet C57BL/6 mouse in 2mo had showed general symptoms of diabetes: polydipsia, polyphagia, polyuria, weight loss etc. The model had a steady-state high glucose (≥18mmol/L), also the weight was lower compared with normal control mouse. 1% rose bengal corneal staining had dot coloring at 2mo after completion of the model, the stained area and extent were gradually increased with the extension of the duration of diabetes, almost all the cornea was stained at 12mo after completion of the
model. With the passage of time into a mold, the cornea epithelial healing time become longer: 2mo was about 40h;3mo was about 120h; 4, 6, 12mo was about 144h;the coloboma were gradually increased at 12mo after completion of the model, then the area was reduced gradually until complete healing, the time was 96~120h, showed repeating phenomenon.
CONCLUSION: The mouse were induced by high-fat and high-glucose diet can be used as animal models of diabetic keratopathy: the damage of epithelium for corneal and delay healing on epithelium and other symptoms.

Emergencies ; Environmental Exposure ; standards ; Humans ; Maximum Allowable Concentration

China ; Foundations ; Preventive Medicine ; economics ; Research Support as Topic ; statistics & numerical data

The RAS (rat sarcoma) gene is one of the important oncogenes, and its mutation is present in about 30% human tumors. KRAS (kirsten rat sarcoma viral oncogene) is one of the three RAS subtypes, and KRAS mutations are more common than the mutations in other two RAS subtypes. In recent years, with the continuous research, new ideas have been provided for the treatment of cancers via targeting-KRAS. Efforts have been made to develop various KRAS inhibitors. Here, based on the mechanism of action, we classified KRAS inhibitors into two categories: inhibitors that directly target KRAS and inhibitors that indirectly act on KRAS. The representative KRAS inhibitors were summarized and introduced in this paper.

Indoleamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the degradation of tryptophan to kynurenine. IDO1 is highly expressed in some tumor tissues. IDO1 can deplete tryptophan in tumor microenvironment, inhibit T cell function, and mediate the immune escape of tumor cells. Thus, IDO1 is considered a potential target of tumor immunotherapy. Currently, there are several IDO1 inhibitors in clinical research studies. The mechanism of IDO1-mediated tumor immune escape and the structure of IDO1 inhibitors are summarized in this review.

Cell Transformation, Neoplastic ; drug effects ; genetics ; Dimethyl Sulfoxide ; pharmacology ; Electroporation ; methods ; HL-60 Cells ; Humans ; Membrane Proteins ; genetics ; Neoplasm Proteins ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Stromal Interaction Molecule 1 ; Transfection

The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

Objective To explore the influence of hemodialysis(HD) and henodiafiltation on serum ?_2-microglobulin(?_2-MG) of children with acute renal failure and contrast research on declining rate of serum ?_2-MG before and after(children′s) HD and HDF.(Met-)hods By Branc Dialog HD machine of double-pump,HDF for 18 times and HD for 20 times were given to children with acute renal(fai-)lure.The serum ?_2-MG were observed before and after HD and HDF.Results A great difference was observed in level of serum ?_2-MG between before and after HD and HDF.In HDF group,there was significant difference in level of serum ?_2-MG before and after HDF(P

Human neutrophil elastase (hNE) is a serine proteolytic enzyme mainly distributed in neutrophils. When the balance between anti-hNE protein and hNE is broken, excessive release of hNE can cause the occurrence of various diseases. Therefore, inhibition of hNE is a promising therapeutic strategy. In this paper, the structure, action mechanism, physiological function of hNE and the development of hNE inhibitors were briefly summarized, in order to provide information for the related research.

0.05).Conclusions SNP of 2350G→A in ACE gene is associated with MI,AA genotype is probably a genetic marker of MI in Han nationality.