Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases.

E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play key roles in protein degradation. However, a large number of E3 substrate interactions (ESIs) and DUB substrate interactions (DSIs) remain elusive. Here, we present DeepUSI, a deep learning-based framework to identify ESIs and DSIs using the rich information present in protein sequences. Utilizing the collected golden standard dataset, key hyperparameters in the process of model training, including the ones relevant to data sampling and number of epochs, have been systematically assessed. The performance of DeepUSI was thoroughly evaluated by multiple metrics, based on internal and external validation. Application of DeepUSI to cancer-associated E3 and DUB genes identified a list of druggable substrates with functional implications, warranting further investigation. Together, DeepUSI presents a new framework for predicting substrates of E3 ubiquitin ligases and deubiquitinates.

CF3SO2Na-Mediated, UV-Light-Induced Friedel-Crafts Alkylation of Indoles with Ketones/Aldehydes and Bioactivities of Products.

A concise, one-step route to produce 3,3'-diindolylmethanes (DIMs) from simple indoles and ketones or aldehydes is reported. The key step is the ready formation of indole derivatives that involves the in situ conversion of CF3SO2Na reagent to ·CF3 under oxygen or air (1.0 atm) and UV irradiation. It is disclosed that most of the obtained DIMs show anticancer activities in human bladder cancer cell lines EJ and T24.

Evaluation of the effect of a toothpaste containing Pudilan extract on inhibiting plaques and reducing chronic gingivitis: A randomized, double-blinded, parallel controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan is a famous traditional Chinese medicine compound which contains several Chinese herbal ingredients, and has been wildly used to treat a variety of inflammatory diseases in China. Recently, it was reported that Pudilan extract had been used in the oral field, especially in the treatment of minor oral ulcers for its anti-inflammatory, pain relieving, antibacterial, clearing heat, and detoxifying effects. AIM OF THE STUDY: To evaluate the effectiveness and safety of Pudilan extract-containing toothpaste in controlling plaques and reducing chronic gingivitis. MATERIALS AND METHODS: A total of 120 patients with chronic gingivitis were randomized into an experiment group and a control group (n = 60 patients per group) based on a double-blinded method. Patients in the experiment group used a Pudilan extract-containing toothpaste, whereas patients in the control group used a Pudilan toothpaste simulator, which were identical as the toothpaste used by the experiment group, except for not containing the Pudilan extract. The Plaque Index (PI), Gingival Index (GI), Bleeding Index (BI), and Bleeding On Probing proportion (BOP%) were recorded at baseline, 4 weeks, 8 weeks and 12 weeks after using the toothpaste. RESULTS: After using the toothpaste for 8 and 12 weeks, PI, BI, GI, and BOP% of the experiment group were significantly lower when compared to the control group (both p < 0.001). Moreover, after using the toothpaste for 4, 8, and 12 weeks, the decline of the PI and GI in the experiment group were significantly higher than the control group (p < 0.001, except 4weeks PI p = 0.011). After 12 weeks, the PI of the experiment group decreased 35.73% (p < 0.001) whereas the GI decreased 29.04% (p < 0.001). BI and BOP decline rates were statistically significant when compared to those of the control group at 8 and 12 weeks (both p < 0.001). Moreover, at 12 weeks, the BI of the experiment group decreased 34.33% (p < 0.001) and BOP% decreased 54.71% (p < 0.001). CONCLUSION: Toothpaste with Pudilan extract demonstrated good effect on relieving symptoms of chronic gingivitis by inhibiting plaque formation, reducing gingival inflammation and the degree of bleeding, and the bleeding rate. Toothpaste containing Pudilan extract has prospective application potentials in the prevention and treatment of chronic gingivitis.

Effect of cyclic uniaxial compressive stress on human dental pulp cells in vitro.

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.