Novel Coumarin-furo[2,3-d]pyrimidinone hybrid derivatives as anticancer agents: Synthesis, biological evaluation and molecular docking.

A series of coumarin-furo[2,3-d]pyrimidinone hybrid derivatives were synthesized, characterized by HR-MS, 1H NMR and 13C NMR. All synthesized compounds were evaluated for antiproliferative activities against hepatic carcinoma (HepG2) and cervical carcinoma (Hela) cell lines in vitro, and results shown that most of the compounds exhibited potent antitumor activity. Moreover, compound 3i, 8d and 8i were selected to induce apoptosis in HepG2 cells, and it displayed a significant concentration-dependent. Further, transwell migration assay was used to detect the most potent compound 8i, and the results revealed that 8i can significantly inhibit HepG2 cells migration and invasion. In addition, kinase activity assay showed compound 8i may be a multi-target inhibitor, which 8i has an inhibition rate of 40-20% on RON, ABL, GSK3α and so on ten different kinases at the concentration 1 µmol/L. At the same time, molecular docking studies revealed the possible binding modes of compounds 3i, 8d and 8i with kinase recepteur d'origine nantais (RON). A comparative molecular field analysis (CoMFA) model was established from 3D-QSAR study that guide us to a more bulkly and electro-positive Y group at the C-2 position of furo[2,3-d]pyrimidinone ring was preferable for the bioactivity improvement of our compounds. Our preliminary research indicated that the coumarin skeleton introducing to the furo[2,3-d]pyrimidine system had a significantly influence on the biological activities.

Assessment and modeling of effluent quality, economic benefits, and greenhouse gas reduction for receiving brewery wastewater on A2O by GPS-X.

Recently, breweries have been allowed to discharge brewery wastewater (BWW) to the sewage pipe network to alleviate the shortage of carbon sources of municipal wastewater treatment plants (MWTPs) under the premise of signing a contract with MWTPs in some countries. This study aims to provide a model-based method for MWTPs to evaluate the threshold, the effluent risk, the economic benefits, and the potential greenhouse gas (GHG) emissions reduction of receiving BWW. In this research, a simulation model of an anaerobic-anoxic-oxic process (A2O) receiving BWW was established based on the data of a real MWTP and brewery using GPS-X. The sensitivity factors of 189 parameters were analyzed, and several sensitive parameters were calibrated stably and dynamically. By analyzing the errors and standardized residuals, the calibrated model was proved to be high-quality and reliable. In the next phase, the impact of receiving BWW on the A2O was evaluated in terms of effluent quality, economic benefits, and GHG emissions reduction. The results showed that receiving a certain amount of BWW can effectively reduce the carbon source cost and GHG emissions for the MWTP compared with adding methanol. Though the chemical oxygen demand (COD), biochemical oxygen demand in five days (BOD5), and total nitrogen (TN) in the effluent increased in various degrees, the effluent quality still met the discharge standard implemented by the MWTP. The study can also facilitate the modeling work for many researchers and promote more kinds of food production wastewater to be treated equally.

Early assessment of acute ischemic stroke in rabbits based on multi-parameter near-field coupling sensing.

BACKGROUND: Early diagnosis and continuous monitoring are the key to emergency treatment and intensive care of patients with acute ischemic stroke (AIS). Nevertheless, there has not been a fully accepted method targeting continuous assessment of AIS in clinical. METHODS: Near-field coupling (NFC) sensing can obtain the conductivity related to the volume of intracranial components with advantages of non-invasiveness, strong penetrability and real-time monitoring. In this work, we built a multi-parameter monitoring system that is able to measure changes of phase and amplitude in the process of electromagnetic wave (EW) reflection and transmission. For investigating its feasibility in AIS detection, 16 rabbits were chosen to establish AIS models by bilateral common carotid artery ligation and then were enrolled for monitoring experiments. RESULTS: During the 6 h after AIS, the reflection amplitude (RA) shows a decline trend with a range of 0.69 dB and reflection phase (RP) has an increased variation of 6.48° . Meanwhile, transmission amplitude (TA) and transmission phase (TP) decrease 2.14 dB and 24.29° , respectively. The statistical analysis illustrates that before ligation, 3 h after ligation and 6 h after ligation can be effectively distinguished by the four parameters individually. When all those parameters are regarded as recognition features in back propagation (BP) network, the classification accuracy of the three different periods reaches almost 100%. CONCLUSION: These results prove the feasibility of multi-parameter NFC sensing to assess AIS, which is promised to become an outstanding point-of-care testing method in the future.

NRF2 deficiency increases obesity susceptibility in a mouse menopausal model.

The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females. The mice were divided into four groups according to their genotypes and treatments. Blood samples and bodyweights were obtained preoperatively and in the first to ninth postoperative weeks after overnight fasting. Serum levels of triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose (GLU) were measured at postoperative weeks 0, 1, 3, 5, 7, and 9. Neurotransmitter dopamine (DA) and serotonin (5-HT) was analyzed in brain tissues after sacrifice at postoperative week 9. The results demonstrated that, compared with the corresponding wild-type (WT) mice, KO ovariectomized mice had a greater bodyweight gain (P<0.01). Serum analysis showed that the serum GLU, T-CHO, and TG were significantly lower (P<0.05) but LDL was significantly higher (P<0.05) in the KO control mice than that in WT control mice. However, different from the WT counterparts, an increase in blood GLU level (P<0.05), unchanged T-CHO, TG, and HDL levels, and a significant reduction in LDL (P<0.01) was found in the KO ovariectomized mice. In addition, the level of 5-HT was significantly reduced (P<0.05) in the KO mice after ovariectomy. In conclusion, the combination of Nrf2 deletion and a decline in estrogen level induced a significant increase in bodyweight, which may be associated with their altered glucose and LDL metabolism and decreased 5-HT levels. From a clinical perspective, women with antioxidant defense deficiency may have an increased risk of metabolic abnormalities after menopause.

Isolation and characterization of antiproliferative peptides from Chinese three-striped box turtle (Cuora trifasciata).

In this study, the whole proteins from a Chinese three-striped box turtle (Cuora trifasciata) were extracted and hydrolyzed using three proteases (alcalase, papain, and protamex). By orthogonal experiments, the optimal hydrolysis conditions for producing peptides with the highest cancer cells growth inhibition activity were determined. Such as, the maximum inhibition on MCF-7 cancer cells (92.37% at 1 mg/mL) was achieved by papain hydrolysis (pH 8, 37 °C, enzyme-to-substrate ratio (E/S) 1.5%), and the maximum inhibition on HepG2 cancer cells (94.16% at 1 mg/mL) was reached by protamex hydrolysis (pH 8, 40 °C, E/S 2%). Using ultrafiltration and Sephadex G-15 column chromatography, two polypeptides M2 and F4 were isolated. At 500 µg/mL, M2 exhibited 74.7% and 62.9% of antiproliferation activities on MCF-7 and HepG2 cancer cells, respectively; and F4 displayed good inhibitory effects on MCF-7 (70.59%) and HepG2 (78.6%) cancer cells. M2 and F4 had lower inhibition (<20%) than drug 5-FU (>60%) on normal liver cells L-O2. Moreover, three peptides, EMLQPPL, PGKPLFL, and SCCSCDED, were identified; their inhibitory effects on cancer cells were confirmed after synthesis. These data, for the first time, demonstrated that Cuora trifasciata-derived proteins could be used for preparing antiproliferation peptides.

Separation and nanoencapsulation of antitumor peptides from Chinese three-striped box turtle (Cuora trifasciata).

Chinese three-striped box turtle (Cuora trifasciata), as a freshwater turtle, is used as a tonic food. The purpose of this study was to isolate peptides with cancer growth inhibition activity from trypsin-digested hydrolysates of turtle proteins. The results demonstrated that two fractions T1 and T2 exhibited good inhibition on HepG-2 and MCF-7 cancer cells, with an inhibition of 70.65-89.1%, at 500 µg/mL. Subsequently, three peptides were identified from T1 and T2, including RGVKGPR (T1-1), KLGPKGPR (T1-2), and SSPGPPVH (T2-1). By database search, T2-1 was a completely new peptide; its inhibition activity on MCF-7 cancer cells was the best, up to 70.02% at 500 µg/mL. Then, T1 and T2-1 were nanoencapsulated by chitosan. After nanoencapsulation, the inhibition percentages were 50.23% for the nanoencapsulated T1 on HepG-2 and 46.82% for the encapsulated T2-1 on MCF-7. The release experiment indicated that the encapsulated peptides could be slowly released in simulated gastrointestinal juice.