ABSTRACT
The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.
ABSTRACT
CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.
ABSTRACT
Objective To explore the reconstruction effects of lower hemifascial scar by cervical skin excessive volume expansion. Methods Single 100 ml or 150 ml standard volume tissue expander was implanted under the cervical skin in 50 patients with lower hemifascial scar. After the tissue expanders were injected with 4-5 times than the designed volume, the scar was resurfaced with the expanded flap. Results The excessively expanded cervical flaps of 50 patients all were successfully used to reconstruct the facial scar. The expanded flap was matched well with surrounding skin after 3-12 months following-up. No obvious contracture was observed. The district recontrueted by expended flaps have the normal expression aetivities. Conclusion Excessive expansion of cervical skin can promote the efficiency in the reconstruction of the lower hemifascial scar.
ABSTRACT
OBJECTIVE:To study the possible mechanisms of the effects of indol-2,3-dione (MW147) on experimental atherosclerosis (AS). METHODS: A total of 120 male quails were randomly divided into six groups: normal control group, model group, lovastatin (79.5 mg?kg-1) positive control group, and MW147 (20, 60, 120 mg?kg-1) groups. The normal control group was fed on normal diet, while the other 5 groups were fed on high lipid diet and treated ig with corresponding drugs for eight weeks. Then the lipid levels including TC, TG, L-DLC and H-DLC in serum and tissues, and the total superoxidedismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) were determined. Meanwhile the tissues of aorta and liver were observed under light microscope. RESULTS: In MW147-treated groups compared with model group, the levels of TC, TG, LDL-C and MDA were decreased while the levels of HDL-C, T-SOD, GSH-Px and T-AOC in serum were increased (P