Prenylated flavonoid fractions from Glycyrrhiza glabra alleviate insulin resistance in HepG2 cells by regulating the ERK/IRS-1 and PI3K/Akt signaling pathways.

Insulin resistance (IR) is a key factor in the pathogenesis of disrupted glucose metabolism. Although the extract of Glycyrrhiza glabra has shown significant hypoglycemic activity, its bioactive components remain to be identified, and their mechanisms of action, especially on hepatocyte glucose metabolism, are yet to be explored. In the present study, the primary compounds from Glycyrrhiza glabra [named prenylated flavonoid fractions (PFFs)] have been identified and their chemical structures have been elucidated. The therapeutic effects of PFFs extracted from G. glabra on glucose metabolism disorders and IR in high insulin-induced insulin-resistant HepG2 (IR-HepG2) cells have been determined. Glabridin (GLD) was used as a control. The results indicated that, similar to GLD, PFFs increased glucose consumption, glucose uptake, and translocation of glucose transporter 4 to the plasma membrane in IR-HepG2 cells. In addition, they enhanced the activities of glycogen synthase, glucokinase, and pyruvate kinase, while reducing the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Furthermore, they activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and suppressed the extracellular signal-regulated kinase/insulin receptor substrate-1 (ERK/IRS-1) pathway. These findings suggest that, similar to GLD, PFFs can alleviate impaired glucose metabolism and alleviate IR in IR-HepG2 cells.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.The authors and their affiliations have been confirmed as correct.

An Evaluation Model of Agricultural Entrepreneurial Ecological Environment Quality Oriented to Public Health Topic Using the Optimized Neural Network Algorithm.

As the primary industry, agriculture is a prerequisite for human survival and a basic industry of the national economy. As a result, the growth of agriculture is vital for the nation's socioeconomic development. The construction of ecological civilization and the reform and innovation of farmers' digital entrepreneurial behavior in the region are intimately correlated with the agricultural eco-environmental quality. Therefore, it is crucial for us to improve control and maintenance of the agricultural eco-environment. A requirement for directing the sustainable growth of the agricultural economy is evaluating and identifying the quality of the regional eco-environment and the issues it faces. In view of this, the study employs Jiangsu Province as a research example, builds a comprehensive index evaluation system, and uses the modified BP neural network to evaluate the agricultural eco-environmental quality in the target area between 2010 and 2020. First, the evaluation system is constructed from four dimensions: ecological resource status, environmental pollution degree, eco-environmental protection efforts, and agricultural development level, and 14 influencing factors are then screened out as specific secondary evaluation indicators. Second, a GA-BP model will be applied to comprehensively assess the quality of the agricultural eco-environment in the province over the past 10 years. The comprehensive score of the province's agricultural eco-environmental quality was calculated, and the quality level was classified by this. Meanwhile, the indicators' scores were paired with an analysis of each contributing factor's degree of change. The findings indicate that from 2010 to 2020, Jiangsu Province's agricultural eco-environment demonstrated a favorable trend, a reasonably high-quality level, and a tendency of continuous improvement from bad to good. The results of each indicator measuring the quality of the agricultural environment fluctuated, but overall they showed an upward trend. Finally, in order to offer a reference for agricultural eco-environment control and protection and a good ecological environment for farmers' digital entrepreneurship in the near future, countermeasures and suggestions are proposed for the restoration of the agricultural eco-environment in Jiangsu Province referring to the results of the research and the problems already present in the area.

Screening and identification of a novel antidiabetic peptide from collagen hydrolysates of Chinese giant salamander skin: network pharmacology, inhibition kinetics and protection of IR-HepG2 cells.

In this study, a novel peptide GPPGPA was screened from the collagen hydrolysates of Chinese giant salamander (Andrias davidianus) skin, and its anti-diabetes mechanism was predicted by network pharmacology, and an inhibitory effect on α-glycosidase and protective effect on IR (insulin resistance) and oxidative stress of IR-HepG2 cells were detected. Through network pharmacology screening, GPPGPA was found to have good drug-like properties, and 103 targets of GPPGPA overlap with T2DM targets. These targets were mainly enriched in the PI3K-Akt signaling pathway associated with T2DM, the AGE-RAGE signaling pathway in diabetic complications, the TNF signaling pathway, insulin resistance and so on. The core targets were identified as AKT1, MAPK8, MAPK10 and JUN by constructing a "peptide-target-pathway" network. The molecular docking results showed that GPPGPA was well bound to the core targets. These results suggested that GPPGPA had the potential to reduce T2DM. Further in vitro experiments showed that GPPGPA as a competitive inhibitor could effectively inhibit the activity of α-glucosidase. The results of the IR-HepG2 cell model experiments showed that GPPGPA was not toxic to HepG2 cells, and could reduce IR of HepG2 cells induced by high-glucose and high-insulin, improve glucose consumption, increase the activity of superoxide dismutase (SOD), and reduce the content of malondialdehyde (MDA). The above results suggested that GPPGPA could improve T2DM by reducing insulin resistance through a multi-target and multi-pathway mechanism. GPPGPA could be developed and utilized as a novel hyperglycemic inhibitor in functional food.

The Evaluation Model of College Students' Mental Health in the Environment of Independent Entrepreneurship Using Neural Network Technology.

In recent years, the employment of college students is becoming more and more prominent; no matter for the society, universities, college students themselves, and their families have formed a huge pressure, in the current situation, the success rate of college students to start their own business is not high; one of the important reasons is that college students generally have defects in entrepreneurial psychology. Therefore, effective evaluation of college students' mental health under the environment of independent entrepreneurship is conducive to comprehensively improving the quality of talent training in colleges and universities. In this paper, we propose a novel three-channel multifeature fusion network based on neural network technology to identify and predict college students' mental health problems in the self-entrepreneurship environment. Specifically, we first extract the behavior characteristics, visual characteristics, and social relations as a three-channel network input. Second, in view of the behavior characteristic, we use the length of the memory deep context dependent on network access. In view of visual features, we use the convolution neural network to face emotional characteristics and characteristics of social relations. The feature concat strategy is used for feature fusion. The experimental results on real datasets show that the method in this paper is effective, and it is expected to propose a new solution for college students' mental health assessment.

Effects of konjac glucomannan on the water distribution of frozen dough and corresponding steamed bread quality.

The influences of konjac glucomannan (KGM) on the water distribution of frozen dough and steamed bread quaility made from frozen dough were addressed in this study. Low Field Nuclear Magnetic Resonance (LF-NMR) analysis demonstrated that the less tightly bound water of the dough was transferred to tightly bound water with the increase of KGM. Differential Scanning Calorimetry (DSC) showed that the freezable water of the frozen dough was transferred to non-freezable water with increasing the amount of KGM. DSC and LF-NMR results indicated the water state in the frozen dough was consistent. The addition of KGM enhanced the height and whiteness of steamed bread, but it decreased springiness, cohesiveness and resilience of steamed bread. As the KGM substitution rate increased, the hardness of steamed bread first decreased and then increased. The steamed bread with 1.5% of KGM showed the best quality.

Effects of aspirin on hepatocellular carcinoma and its potential molecular mechanism.

PURPOSE: To explore the effects of aspirin (ASP) on the proliferation and apoptosis of HepG2 hepatocellular carcinoma (HCC) cells via the Wnt/ß-catenin signaling pathway. METHODS: Human HCC cells were cultured and treated with ASP at different concentrations. Cell proliferation was determined with cell counting kit-8 (CCK-8) and colony formation, and the rate of apoptosis was measured by flow cytometry. Western blotting (WB) and quantitative polymerase chain reaction (qRT-PCR) assays were used to assess the changes in the expression levels of related proteins. RESULTS: ASP showed a time-and concentration-depented inhibitory effect on HepG2 cell proliferation. The number of colonies formed in ASP-treated HCC cells was significantly lower than in control cells. For HCC cells treated with ASP, the apoptosis rate enhanced with the increase of ASP concentration. The expression levels of TCF4 and LEF1, key molecules of the Wnt/ß-catenin signaling pathway, were lowered in HCC cells treated with 4 mM ASP, and the nuclear translocation of ß-catenin was weakened. The ß-catenin activator exerted a negative influence on the anticancer effect of ASP. CONCLUSIONS: ASP inhibits the proliferation and promotes the apoptosis of HCC cells through the Wnt/ß-catenin signaling pathway.

Interaction mechanism of aloe-emodin with trypsin: molecular structure-affinity relationship and effect on biological activities.

The molecular mechanism of interaction between aloe-emodin (AE) and trypsin was investigated, exhibiting remarkable outcomes. To detect the interaction mechanism, the binding of AE with trypsin was examined by a multi-spectroscopy and molecular docking method. Results showed that the binding of AE and trypsin would lead to static quenching and their binding forces were van der Waals forces and hydrogen bonding. The results of simultaneous and three-dimensional fluorescence spectroscopy showed that the combination of AE and trypsin caused changes in the microenvironment around the trypsin fluorophore, which might change the spatial structure of trypsin. FT-IR spectroscopy showed that the contents of α-helix and ß-turn in trypsin were decreased and the contents of ß-sheet, random coil and antiparallel ß-sheet were increased. Moreover, all these experimental results were verified and reasonably explained by molecular docking results. We also investigated the enzyme activity of trypsin and the antioxidant activity of AE. The results showed that both the enzyme activity of trypsin and the antioxidant activity of AE were decreased after interaction between AE and trypsin. The findings outlined in this study should elucidate the molecular mechanisms of interaction between AE and trypsin and contribute to making full use of AE in the food industry.

In Vitro Antioxidant Activity of Peptides from Simulated Gastro-Intestinal Digestion Products of Cyprinus carpio haematopterus Scale Gelatin.

A two-stage simulated gastro-intestinal (GI) digestion model (2 h pepsin treatment and subsequent 2 h pancreatin treatment at 37 °C) was used to explore the antioxidant activity of the digested products of Cyprinus carpio haematopterus scale gelatin with different molecular weights (MW). From the gastric phase to the intestinal phase, the hydrolysis degree of the products increased from 2.6 ± 0.4% to 16.9 ± 0.7%. The fraction of 0-1 kDa (JCP3) exhibited the best antioxidant activities in hydroxyl radical scavenging, reducing power, and metal chelating activity. The fraction of 1-3 kDa (JCP2) exhibited the best 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. However, the fractions of 0-1 kDa (JCP3) and 1-3 kDa (JCP2) showed similar inhibitory activity of lipid peroxidation. The results indicated that Cyprinus carpio haematopterus scale gelatin can be digested in the gastrointestinal tract. Furthermore, the digested products had antioxidant activity.

Molecular mechanism of the interaction between resveratrol and trypsin via spectroscopy and molecular docking.

The molecular mechanism of the interaction between resveratrol and trypsin was studied using fluorescence spectroscopy (intrinsic fluorescence, synchronous fluorescence, three-dimensional fluorescence), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and the molecular docking method, as well as through enzyme activity and antioxidant assay. The fluorescence experiments (the Stern-Volmer quenching constants (KSV)) indicated that resveratrol quenched the intrinsic fluorescence of trypsin through the static quenching mechanism. The number of binding sites was about one. The thermodynamic functions ΔG < 0 and ΔH > 0, ΔS > 0 of the binding process, indicating that the combination of the resveratrol and trypsin processes was a spontaneous exothermic reaction and that the hydrophobic effect was the main force between them. UV-vis spectra, synchronous fluorescence spectra and three-dimensional fluorescence spectra analysis showed that the combination of resveratrol and trypsin induced changes in the microenvironment around the fluorophores of trypsin, resulting in alterations in the spatial structure of trypsin. FT-IR spectroscopy indicated that the contents of the α-helixes and ß-turns in trypsin decreased and that the contents of the ß-sheets, random coils and antiparallel ß-sheets increased. All these experimental results were verified and reasonably explained by the molecular docking results. Upon resveratrol and trypsin binding, the enzyme catalytic activity of trypsin and the antioxidant of resveratrol decreased. Results from this study would be useful in elucidating the molecular mechanisms of the interactions between resveratrol and trypsin and contribute to making full use of resveratrol in the food industry.

[Response of Nostoc flageliforme cell to Cu2+, Cr2+ and Pb2+ stress].

OBJECTIVE: This study aimed to investigate the effects of Cu2+, Cr2+ and Pb2+ stress on Nostoc flagelliforme cell. METHODS: The response of Nostoc flagelliforme cell was analyzed under the stress. The modified BG11 culture medium containing different heavy metal ions of 0, 0.1, 1.0, 10, 100 mg/L was used to cultivate Nostoc flagelliforme cell at 25 degrees C and light intensity of 80 micromol/(m x s). Electrolyte leakage, the activities of superoxide dismutase, the content of malondialdehyde, proline, soluble protein and trehalose were analyzed. RESULTS: Under 1 - 100 mg/L Cu2+, Cr2+ and Pb2+ stress, electrolyte leakage and malondialdehyde contents in Nostoc flagelliforme cell were higher than those in the control group during heavy metal ions stress. Meanwhile, superoxide dismutase activity increased slightly under 10 mg/L, but was lower afterwards. The contents of proline, soluble protein and trehalose increased under 10 mg/L heavy metal ions stress, while declined under extreme heavy metal ions stress (100 mg/L). CONCLUSION: Nostoc flagelliforme cell has resistance to low heavy metal ions stress, but is damaged badly under extreme heavy metal ions stress.

Molecular switch for the assembly of lipophilic drug incorporated plasma protein nanoparticles and in vivo image.

A strategy to manipulate the disulfide bond breaking triggered unfolding, and subsequently assembly of human serum albumin (HSA) in a lipophilic drug-dependent manner is present. In this study, the hydrophobic region, a molecular switch of the HSA, was regulated to form HSA-paclitaxel (HSA-PTX) nanoparticles by a facile route. High-resolution transmission electron microscopy and fluorescence quenching indicate that HSA coassembled with PTX, which acts as a bridge to form core-shell nanoparticles about 50-240 nm in size, and that PTX might bind to the subdomain IIA sites of HSA. Change of ultraviolet absorption and circular dichroism spectra reveal the formation of HSA-PTX nanoparticles, which is a safety, injectable pharmaceutic nanocarrier system for tumor target. This method to prepare nanocarrier systems for hydrophobic guest molecules reveals a general principle of self-assembly for other plasma proteins and other pharmacologically active substances with poor water solubility. It also provides a basis for developing nanocarrier systems for a wide range of applications in nanomedicine, from drug delivery to bioimaging systems.

Sustained delivery of endostatin improves the efficacy of therapy in Lewis lung cancer model.

The purpose of this work was to develop an effective delivery system for antiangiogenic therapy. Endostatin was microencapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by using a w/o/o multiple emulsification-evaporation technique. Endostatin microspheres showed the encapsulation efficiency 100% with mean particle size about 25 microm. Endostatin released in vitro from PLGA microspheres were biologically active and significantly inhibited the migration of endothelial cells. In rats, endostatin microspheres produced a sustained release process in which the steady-state concentration was reached from day 5 to day 27 with the steady-state levels of endostatin between 174.8+/-33.3 and 351.3+/-126.3 ng/ml. In Lewis lung cancer model, a dose of 10 mg/kg endostatin microspheres was just as effective in suppressing tumor growth as a dose of 2 mg/kg/day free endostatin for 35 days (total dose 70 mg/kg). These results indicated PLGA microspheres further reduced the amount of endostatin needed to achieve significant tumor inhibition in mice when compared with systemic administration.

A simple method for obtaining transferrins from human plasma and porcine serum: preparations and properties.

A simple method was described for the purification of serum transferrin (Tf) from human plasma and porcine serum with relative high yield and purity. The properties including purity, integrity, immunoreactivity and the receptor-binding ability of the proteins were studied by several assays, comprising spectrometry, SDS-PAGE, HPLC, Western blotting, urea electrophoresis, mass spectrometry and cytometry. Analysis from all the different aspects manifested that the proteins were of high purity. The two kinds of Tfs appeared to be iron-saturated as confirmed by their absorbance spectra and urea-PAGE mobility. The specific spectra of absorption of the two Tfs were both at around 465 nm. The relative molecular weights of human Tf (hTf) and porcine Tf (pTf) were determined by SDS-PAGE and further identified by MAIDI-TOF mass spectrometry with a result of 79,707 and 79,258, respectively. Immunoblotting assay showed that pTf could react with the anti-human Tf monoclonal antibody with a less level compared to hTf. FACS assays of their binding activities to Tf receptor-positive cell (K562 cell line) indicated that pTf could be recognized by the hTf receptor and internalized into cells, with a slightly less efficacy than hTf. All special property studies demonstrated that pTf was similar to hTf in physical and chemical characteristics, which gave a hint that pTf could substitute for hTf in some kinds of researches, such as using hTf as a carrier in drug targeting system.