Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

The kidney antifibrotic effects of 5,7,3',4',5'-pentamethoxyflavone from Bauhinia championii in streptozotocin-induced diabetic rats: in vivo and in vitro experiments.

CONTEXT: The antidiabetic effects of flavonoids have been reported, but it is still unclear whether 5,7,3',4',5'-pentamethoxyflavone, isolated from Bauhinia championii Benth. (Fabaceae), also exhibits such properties. OBJECTIVE: To isolate 5,7,3',4',5'-pentamethoxyflavone from B. championii using high-speed countercurrent chromatography and examine its potential in treating diabetic nephropathy. MATERIALS AND METHODS: The phytochemical constituents from the stems of B. championii were separated and purified with high-speed countercurrent chromatography; 5,7,3',4',5'-pentamethoxyflavone (PMF) was identified by mass spectrum, 1H-NMR, and 13C-NMR. After exposing mesangial cells to 30 mM glucose and either 5 µM or 10 µM PMF for 6 h, the levels of fibronectin (FN) and p-Smad2/3 were analyzed using Western blotting. Male Sprague-Dawley rats were injected intraperitoneally with 55 mg/kg streptozotocin to induce diabetes and then were randomized into three groups (n = 10): vehicle administration, low-dose (5 mg/kg) PMF, and high-dose (25 mg/kg) PMF by intragastric gavage for 3 months. A healthy group was included as the control. RESULTS: Compared to the diabetic group, low-dose and high-dose PMF treatment decreased the phosphorylation of Smad2/3 by 0.54- and 0.52-fold, and the accumulation of FN decreased by 0.82- and 0.77-fold in vitro; the phosphorylation of Smad2/3 was decreased by 0.39- and 0.37-fold, and the accumulation of FN decreased by 0.47- and 0.40-fold in vivo, respectively. Furthermore, PMF alleviated the glomerular basement membrane thickness and foot process fusion. CONCLUSION: The findings suggest for the first time that PMF may be a promising treatment option for diabetic kidney fibrosis, which warrants additional clinical investigation.

Hapten designs based on aldicarb for the development of a colloidal gold immunochromatographic quantitative test strip.

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106-1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 µg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.

A Decision Tree Model for Analysis and Judgment of Lower Limb Movement Comfort Level.

To address the problem of ambiguity and one-sidedness in the evaluation of comprehensive comfort perceptions during lower limb exercise, this paper deconstructs the comfort perception into two dimensions: psychological comfort and physiological comfort. Firstly, we designed a fixed-length weightless lower limb squat exercise test to collect original psychological comfort data and physiological comfort data. The principal component analysis and physiological comfort index algorithm were used to extract the comfort index from the original data. Secondly, comfort degrees for each sample were obtained by performing K-means++ to cluster normalized comfort index. Finally, we established a decision tree model for lower limb comfort level analysis and determination. The results showed that the classification accuracy of the model reached 95.8%, among which the classification accuracy of the four comfort levels reached 95.2%, 97.3%, 92.9%, and 97.8%, respectively. In order to verify the advantages of this paper, the classification results of this paper were compared with the classification results of four supervised classification algorithms: Gaussian Parsimonious Bayes, linear SVM, cosine KNN and traditional CLS decision tree.

[Fatigue analysis of upper limb rehabilitation based on surface electromyography signal and motion capture].

At present, fatigue state monitoring of upper limb movement generally relies solely on surface electromyographic signal (sEMG) to identify and classify fatigue, resulting in unstable results and certain limitations. This paper introduces the sEMG signal recognition and motion capture technology into the fatigue state monitoring process and proposes a fatigue analysis method combining an improved EMG fatigue threshold algorithm and biomechanical analysis. In this study, the right upper limb load elbow flexion test was used to simultaneously collect the biceps brachii sEMG signal and upper limb motion capture data, and at the same time the Borg Fatigue Subjective and Self-awareness Scale were used to record the fatigue feelings of the subjects. Then, the fatigue analysis method combining the EMG fatigue threshold algorithm and the biomechanical analysis was combined with four single types: mean power frequency (MPF), spectral moments ratio (SMR), fuzzy approximate entropy (fApEn) and Lempel-Ziv complexity (LZC). The test results of the evaluation index fatigue evaluation method were compared. The test results show that the method in this paper has a recognition rate of 98.6% for the overall fatigue state and 97%, 100%, and 99% for the three states of ease, transition and fatigue, which are more advantageous than other methods. The research results of this paper prove that the method in this paper can effectively prevent secondary injury caused by overtraining during upper limb exercises, and is of great significance for fatigue monitoring.

Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide.

Epidermal growth factor receptor (EGFR) is one of the important and valuable drug targets. Overexpression of EGFR is associated with the development of many types of cancer. In this study, three PROTACs small molecules (16a-16c) were designed, synthesized and evaluated for their cytotoxicity against the growth in different NSCLC cell line and the degradation effect. The bioassay results indicated that 16c has a good inhibition in PC9 cells and H1975 cells, and the corresponding IC50 value was 0.413 µM and 0.657 µM, respectively. Western blotting results demonstrated that compound 16c could serve as an effective EGFRdel19-targeting degrader in PC9 cells.