ADT-OH synergistically enhanced the antitumor activity of celecoxib in human colorectal cancer cells.

BACKGROUND: Colorectal cancer is one of the most prevalent cancers in the world, but the research on its prevention, early diagnosis and treatment is still a major challenge in clinical oncology. Thus, there is a pressing requirement to find effective strategies to improve the survival of colon cancer patients. METHODS: Celecoxib has been accounted to be an effective antitumor drug, but may exhibit significant side effects. In recent studies, 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), one of the most commonly used reagents for the synthesis of sustained-release H2 S donors, has also been reported to inhibit cancer progression by affecting processes such as cell cycle, angiogenesis, and apoptosis. Therefore, we evaluated the therapeutic effect of the combination of ADT-OH and celecoxib on colorectal cancer through in vitro and in vivo, hoping to achieve better therapeutic effect and reduce the effect of celecoxib on gastric injury through exogenous administration of H2 S. RESULTS: Our results demonstrated that ADT-OH combined with celecoxib synergistically inhibited the proliferation and migration ability of human colorectal cancer HCT116 cells, altered cell cycle and cytoskeleton, increased intracellular reactive oxygen species (ROS), and promoted cell apoptosis. Noteworthy, in vivo studies also indicated the excellent antitumor therapeutic effect of the combination therapy without apparent toxicity. CONCLUSIONS: In general, our results provide a reasonable combination strategy of low-dose ADT-OH and celecoxib in the preclinical application of colorectal cancer.

A robust local pulse wave imaging method based on digital image processing techniques.

The original diameter velocity loop method (ln(D)U-loop) cannot accurately extract the blood vessel diameter waveform when the quality of ultrasound image data is not high (such as obesity, age, and the operation of the ultrasound doctor), so it is unable to measure the pulse wave velocity (PWV) of the ascending aorta. This study proposes a diameter waveform extraction method combining threshold, gradient filtering, and the center of gravity method. At the same time, the linear regression method of searching for the rising point of the systolic period is replaced by the optimal average of two linear regression methods. This method can also extract the diameter waveform with poor-quality images and obtain a more accurate PWV. In vivo experimental data from 17 (age 60.5 ± 9.2) elderly patients with cerebral infarction and 12 (age 32.5 ± 5.6) healthy young adults were used for processing, and the results showed that the mean PWV using the ln(D)U-loop method was 12.56 (SD = 3.47) ms-1 for patients with cerebral infarction and 6.81 (SD = 1.73) ms-1 for healthy young adults. The PWV results based on the Wilcoxon rank-sum test and calculated based on the improved ln(D)U-loop method were both statistically significant (p < 0.01). The agreement analysis (Bland-Altman analysis) between the QA-loop and ln(D)U-loop methods showed that the mean deviation of the measured PWV was 0.07 m/s and the standard deviation of the deviation was 1.18 m/s. The experimental results demonstrated the effectiveness of the improved ln(D)U-loop method proposed in this paper on poor-quality images. This study can improve the possibility of the ln(D)U-loop method being widely used in the clinical measurement of ascending aortic PWV.

A Novel Heptapeptide with Tyrosinase Inhibitory Activity Identified from a Phage Display Library.

Peptidic inhibition of the enzyme tyrosinase, responsible for skin pigmentation and food browning, would be extremely useful for the food, cosmetics, and pharmaceutical industries. In order to identify novel inhibitory peptides, a library of short sequence oligopeptides was screened to reveal direct interaction with the tyrosinase. A phage displaying heptapeptide (IQSPHFF) was found to bind most strongly to tyrosinase. The inhibitory activity of the heptapeptide was evaluated using mushroom tyrosinase. The results showed that the peptide inhibited both the monophenolase and diphenolase activities of mushroom tyrosinase with IC50 values of 1.7 and 4.0 mM, respectively. The heptapeptide is thought to be a reversible competitive inhibitor of diphenolase with the inhibition constants (Ki) of 0.765 mM. To further investigate how the heptapeptide exerts its inhibitory effect, a docking study between tyrosinase and heptapeptide was performed. The simulation showed that the heptapeptide binds in the active site of the enzyme near the catalytically active Cu ions and forms hydrogen bonds with five histidine residues on the active site. Phage display technology is thus a useful approach for the screening of potential tyrosinase inhibitors and could be widely applicable to a much wider range of enzymes.