Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Novel synthetic method and analgesic activity of tepoxalin / 药学学报

Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain (postoperation, arthritis et. al.) agent. The new method about the use of novel synthesis reagents and the first using ionic liquid as reactive solvent to synthesize tepoxalin were presented in this paper. The ionic liquid can be easily recycled and reused for several runs efficiently. The analgesic activity of tepoxalin was detected by acetic acid test on mice. The analysis of variance showed that oral administration of tepoxalin could significantly inhibit the number of writhing response within 1 hour and prolong the latent time in a dose dependent manner as compared with CMC control group (P < 0.05). At the same time, tepoxalin had the same analgesic activity as diclofenac sodium.

Clonality and Ki-67 protein expression in gastric carcinoma and precancerous lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clonality of gastric carcinoma and precancerous lesions and its relationship with Ki-67 protein expression.</p><p><b>METHODS</b>Formalin-fixed paraffin embedded tissues were collected from 174 cases of gastric endoscopic biopsies and surgical removed specimens. The lesional tissues were isolated by Laser Capture Microdissection. Methylation sensitive restriction enzyme (HpaII) digestion and polymerase chain reaction (PCR) were used to detect the clonality at the polymorphic human androgen receptor gene locus on the X chromosome. PCR products were analyzed by capillary electrophoresis using applied Biosystems 3730 DNA Analyzer. In addition, a two-step immunohistochemical staining EnVision method was used to detect the expression of Ki-67 protein.</p><p><b>RESULTS</b>The frequency of detection of monoclonality and expression rate of Ki-67 were found increased in a stepwise fashion from gastrointestinal metaplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia to intestinal carcinoma (15.63%, 5/32; 22.22%, 10/45; 69.44%, 25/36 and 100.0%, 20/20; respectively). The presence of clonal proliferation was correlated with Ki-67 expression in low grade intraepithelial neoplasia (P < 0.01).</p><p><b>CONCLUSIONS</b>The presence of clonal proliferation and increased Ki-67 are increasingly detected in the lesions along the multi-step gastric carcinogenesis model. Clonal status is associated with the expression rate of Ki-67 to a certain extent, suggesting a combined application of both markers may be useful in assessing early stages of gastric carcinoma.</p>