MiR-29a-3p: a potential biomarker and therapeutic target in colorectal cancer

Cancer is frequently caused by microRNAs, which control post-transcriptional levels of gene expression by binding to target mRNAs. MiR-29a-3p has recently been shown to play a twofold function in the majority of malignancies, including colorectal cancer (CRC), according to mounting evidence. Here, we not only briefly summarize such connection between miR-29a-3p and cancers, but aslo primarily evaluate the miR-29a-3p expression pattern, clinical applicability, and molecular mechanisms in CRC to provide a guide for future studies. This review established the diagnostic and prognostic value of miR-29a-3p abnormalty in a variety of clinical samples for CRC. Furthermore, current molecular mechanisms of miR-29a-3p for regulating cancerous biological processes such growth, invasion, metastasis, the epithelial-mesenchymal transformation process, and immunomodulation through its upstream regulatory factors and downstream targeted genes were briefly explored. More specifically, miR-29a-3p has been linked to a few medications that have been shown to have anticancer benefits. To sum up, miR-29a-3p is a promising biomarker and prospective therapeutic target for the diagnosis and prognosis of CRC, but further research is still needed to establish a theoretical basis for more practical applications (AU)

MiR-29a-3p: a potential biomarker and therapeutic target in colorectal cancer.

Cancer is frequently caused by microRNAs, which control post-transcriptional levels of gene expression by binding to target mRNAs. MiR-29a-3p has recently been shown to play a twofold function in the majority of malignancies, including colorectal cancer (CRC), according to mounting evidence. Here, we not only briefly summarize such connection between miR-29a-3p and cancers, but aslo primarily evaluate the miR-29a-3p expression pattern, clinical applicability, and molecular mechanisms in CRC to provide a guide for future studies. This review established the diagnostic and prognostic value of miR-29a-3p abnormalty in a variety of clinical samples for CRC. Furthermore, current molecular mechanisms of miR-29a-3p for regulating cancerous biological processes such growth, invasion, metastasis, the epithelial-mesenchymal transformation process, and immunomodulation through its upstream regulatory factors and downstream targeted genes were briefly explored. More specifically, miR-29a-3p has been linked to a few medications that have been shown to have anticancer benefits. To sum up, miR-29a-3p is a promising biomarker and prospective therapeutic target for the diagnosis and prognosis of CRC, but further research is still needed to establish a theoretical basis for more practical applications.

Effects of dietary sodium butyrate on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco).

An 8-week feeding trial was conducted to evaluate the effects of sodium butyrate (SB) on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco). Five isonitrogenous and isolipidic diets (420 g/kg protein and 90 g/kg lipid) were formulated to contain 0 (control), 250, 500, 1,000 or 2,000 mg/kg SB. Triplicate groups of 40 fish (BW = 1.26 ± 0.01 g) per tank (300-L cylindrical fiberglass tanks) for each diet were fed to apparent satiation twice daily. Stomach, hepatopancreas and intestine samples were obtained for digestive enzymes activities analyses. A real-time quantitative PCR analysis was performed to determine the relative expression of target of rapamycin (TOR) and lipoprotein lipase (LPL) in the hepatopancreas and intestine. Fish fed the diets supplemented with SB at 500 and 1,000 mg/kg showed significantly higher specific growth rate and significantly lower feed conversion ratio compared to the control (P < 0.05). Dietary SB inclusion did not alter activities of intestinal amylase, creatine kinase and sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), but increased activities of hepatic trypsin, stomachic lipase, intestinal lipase, alkaline phosphatase and γ-glutamyl transpeptidase for fish fed 1,000 mg/kg SB compared to the control (P < 0.05). Intestine length index, intestine somatic index, fold height and muscular thickness of distal intestine were significantly higher in 1,000 mg/kg SB groups compared to the control (P < 0.05). Significantly higher levels of whole-body crude protein, ash, calcium, phosphorus, nutrition retention and relative mRNA of intestinal TOR were observed in 1,000 mg/kg SB group (P < 0.05). Whole-body lipid content and hepatopancreas LPL mRNA expression in 2,000 mg/kg SB group were significantly higher than the control (P < 0.05). Relative mRNA levels of intestinal LPL and hepatopancreas TOR were significantly higher in the 500 mg/kg SB group compared to those in other groups (P < 0.05). The increased growth performance, digestive enzymes and nutrient retention in fish fed the diets supplemented with SB at 500 and 1,000 mg/kg suggests that SB can be a desirable growth promoter as an antibiotic alternative in diets.

Imidazopyridazine hepatitis C virus polymerase inhibitors. Structure-activity relationship studies and the discovery of a novel, traceless prodrug mechanism.

By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodrug mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

(1) H and (13) C NMR assignments of four series bioactive pyrido[4,3-d]pyrimidine derivatives.

The complete (1) H and (13) C NMR assignments of four series pyrido[4,3-d]pyrimidine derivatives were achieved by combination of one and two-dimensional NMR experiments, and the NMR signals of these compounds were analyzed and compared.

Synthesis and cytotoxicity of 8-cyano-3-substitutedalkyl-5-methyl-4-methylene-7-methoxy-3,4-dihydropyrido[4,3-d]pyrimidines.

Synthesis and cytotoxicity of 11 4-methylene pyrido[4,3-d]pyrimidines 5a-k were described. Cytotoxicity assay results showed that some compounds had much stronger antitumor activity than Fluorouracil against KB cell lines. The most active compound 5i exhibited high potency against KB, CNE2, MGC-803 cell lines with IC(50) values of 0.48, 0.15, 0.59 µM, respectively. The preliminary structure-activity relationships indicated that the introduction of benzyl groups bearing electron-donating function groups is favorable for the activity.