Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Asiatic acid attenuates tubular injury in diabetic kidney disease by regulating mitochondrial dynamics via the Nrf-2 pathway.

BACKGROUND: Mitochondrial dynamics plays a crucial role in tubular injury in diabetic kidney disease (DKD). Asiatic acid (AA) has demonstrated renal protective effects in DKD; however, its therapeutic effect on tubular injury in DKD remains unclear. PURPOSE: This study aimed to verify the effects of AA on tubular injury in DKD and underlying mechanisms. STUDY DESIGN: In the present study, the effects of AA on tubular injury were assessed in rats with streptozotocin-induced diabetes and advanced glycation end products (AGEs)-stimulated HK-2 cells models. METHODS: After oral administration with or without AA for ten weeks, body weight and levels of fast blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), urinary albumin, and kidney injury molecule-1 (KIM-1) were detected. Histological analysis was performed to evaluate the renal function of rats. Moreover, the expression of proteins associated with the Nrf-2 pathway and mitochondrial dynamics was analyzed. AGEs-stimulated HK-2 cells were examined to evaluate the tubular protection and the mechanism of AA in vitro. RESULTS: AA remarkably decreased albumin levels, KIM-1 levels in urine, and serum Cr, and BUN levels. In addition, AA prevented tubular injury and mitochondrial injury by regulating the Nrf-2 pathway and mitochondrial dynamics. Furthermore, the effects of AA on mitochondrial dynamics and tubular protection were eliminated after treatment with ML385 (Nrf2 inhibitor). CONCLUSION: These findings suggested that AA might be developed as a potential candidate for the treatment of tubular injury in DKD, and its effects are potentially mediated via the regulation of the Nrf-2 pathway and mitochondrial dynamics.

Prolonged drought regulates the silage quality of maize (Zea mays L.): Alterations in fermentation microecology.

Prolonged drought stress caused by global warming poses a tremendous challenge to silage production of maize. Drought during maize growth and development resulted in altered micro-environment for silage fermentation. How fermentation of silage maize responds to moisture scales remains uncharted territory. In this research, Maize water control trials were conducted and the silage quality and microbial community of drought-affected maize were determined. The results showed that drought stress significantly reduced the dry matter but increased root-to-shoot ratio, soluble sugar and malonaldehyde content in maize. Before fermentation, the crude protein, crude ash and acid detergent fiber contents were significantly increased but the ether extract content was decreased under drought. The crude protein and acid detergent fiber were significantly decreased in the drought affected group after fermentation. Furthermore, water stress at maize maturity stage greatly reduced the number of total bacteria in silage fermentation but increased the proportion of the lactobacillus and lactic acid content of silage. Drought stress alters the microbial ecosystem of the fermentation process and reconstitutes the diversity of the bacterial community and its metabolites. This study provides a theoretical basis for the study of changes in silage fermentation as affected by abiotic stresses.

New triterpenoids from the Cyclocarya paliurus (Batalin) Iljinskaja and their anti-fibrotic activity.

Cyclocarya paliurus, a Chinese herbal medicine and new food resource, contains a triterpenic-acid-rich extract that demonstrated ameliorative effect on diabetic nephropathy (DN). A more in-depth discovery of functional components led to the isolation of seven new triterpenoids including two pentacyclic triterpenes, 1α,2α,3ß,23-tetrahydroxyolean-12-en-28-oic acid and 2α,3ß,22α-tirhydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranoside, and five tetracyclic triterpenoid glycosides (cypaliurusides N-R), together with twelve known compounds from the leaves of C. paliurus. Their structures were determined using a comprehensive analysis of chemical and spectroscopic data. Partial compounds were assessed for anti-fibrotic activities in high-glucose and TGF-ß1 induced HK-2 cells. Compound 16 remarkably decreased the level of fibronectin with an inhibition rate of 37.1%. Furthermore, 16 effectively alleviated the epithelial-mesenchymal transformation (EMT) process by upregulating E-cadherin expression and downregulating α-SMA expression, and it significantly decreased the level of the transcriptional inhibitors (Snail and Twist) of E-cadherin. The discovery of anti-fibrotic compounds from C. paliurus provides the potential utilization and functional candidates for the DN prevention.

Determination of aldehydes in water samples by coupling magnetism-reinforced molecular imprinting monolith microextraction and non-aqueous capillary electrophoresis.

Excess 2, 4-dinitrophenylhydrazine (2, 4-DNPH) is often applied for the derivatization of aldehyde prior to the chromatographic analysis. However, the residual 2, 4-DNPH may cause background interference and limit the enrichment efficiency of trace aldehydes. To overcome the above bottle-neck problems, improve the extraction efficiency and omit the manipulation for changing the polarity of solvent for the hydrophobic analytes separation, a new method combining magnetism-reinforced in-tube solid phase microextraction (IT-SPME) technique with non-aqueous capillary electrophoresis (NACE) was developed. The monolithic extraction cartridge was prepared in situ inside a capillary and doped with magnetic molecular imprinting polymers (mMIPs). The selective and efficient extraction of the derived analytes with simultaneous removal of the superfluous derivatization agent was achieved owing to the combined effect of molecular imprinting and magnetism reinforcement. By coupling with NACE, the highly hydrophobic effluent can be analyzed directly. The LODs of the method are between 0.0032~0.0049 mg L-1 and the recoveries are between 87.3~99.8% for the tested aldehydes. The developed approach is sensitive enough for detection of surface (drinking) water. The aldehydes in real water samples have been detected by this method, showing results that are in good agreement with the standard SPE-HPLC method.

[Determination of carbonyls in ambient PM2.5 by coupling dummy template imprinting technology and high performance liquid chromatography].

The determination of ambient carbonyls by the derivative method inevitably leads to the introduction of extra 2,4-dinitrophenylhydrazine (2,4-DNPH) into the sample solution. Traditional solid phase extraction (SPE) materials cannot remove this interference. To address this issue, a selective molecularly imprinted solid phase extraction (MISPE) column was prepared. With 2,4-dinitroaniline (2,4-DNAN) as the dummy template, MISPE could eliminate the excessive derivative agent (2,4-DNPH) in the air samples. Consequently, the sample could be concentrated effectively while the sensitivity increased greatly. By coupling MISPE and high performance liquid chromatography (HPLC), the developed method was used to study the concentration and source of 14 carbonyls of PM2.5 during spring in Guangzhou Higher Education Mega Center. Results showed that the total concentration of carbonyls increased with the level of air pollution. Particularly, the content of isovaleraldehyde increased sharply to account for 21% of the 14 total carbonyls in the haze days. Moreover, a high positive correlation between isovaleraldehyde and propionaldehyde was found either in normal days or haze days. From the correlation analysis, it was shown that anthropogenic emissions together with photochemical reaction had contributed to the abnormally high levels of carbonyls in ambient PM2.5 in the haze days. This aspect should be further investigated.

The visual detection of anesthetics in fish based on an inverse opal photonic crystal sensor.

A novel smart sensor for the rapid and label-free detection of benzocaine has been developed based on the combination of photonic crystal (PC) and molecular imprinting polymer (MIP) techniques. A molecularly imprinted photonic crystal (MIPC) hydrogel film was prepared via a non-covalent, self-assembly approach with a PC mould. With a highly ordered inverse opal structure, the resulting benzocaine MIPC exhibited high sensitivity, smart specificity, quick response times and good regeneration abilities. It can give rise to a readable optical signal and color change upon binding with benzocaine, with a detection limit of 16.5 µg mL-1. The sensor has been successfully used to visually estimate benzocaine concentrations in fish samples. In comparison with HPLC, the developed MIPC sensor has shown satisfactory accuracy in terms of results. It has great potential for on-site screening and the visual detection of trace benzocaine in real samples.

Targeting the Golgi apparatus to overcome acquired resistance of non-small cell lung cancer cells to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) were demonstrated to provide survival benefit in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR; however, emergence of acquired resistance to EGFR-TKIs has been shown to cause poor outcome. To overcome the TKI resistance, drugs with different mode of action are required. We previously reported that M-COPA (2-methylcoprophilinamide), a Golgi disruptor, suppressed the growth of gastric cancers overexpressing receptor tyrosine kinases (RTKs) such as hepatocyte growth factor receptor (MET) via downregulating their cell surface expression. In this study, we examined the antitumor effect of M-COPA on NSCLC cells with TKI resistance. As a result, M-COPA effectively downregulated cell surface EGFR and its downstream signals, and finally exerted in vivo antitumor effect in NSCLC cells harboring secondary (T790M/del19) and tertiary (C797S/T790M/del19) mutated EGFR, which exhibit acquired resistance to first- and third generation EGFR-TKIs, respectively. M-COPA also downregulated MET expression potentially involved in the acquired resistance to EGFR-TKIs via bypassing the EGFR pathway blockade. These results provide the first evidence that targeting the Golgi apparatus might be a promising therapeutic strategy to overcome the vicious cycle of TKI resistance in EGFR-mutated NSCLC cells via downregulating cell surface RTK expression.