Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes. / èŽ²é›¾å¤šç³–å¯¹æ°¨åŸºç”²é ¸ä¹™é ¯è¯±å¯¼äººè‚ç»†èƒžæ°§åŒ–æŸä¼¤çš„æŠ‘åˆ¶ä½œç”¨ç ”ç©¶.

Wax apple (Syzygium samarangense) has received growing research interest for its high nutritional and medicinal value due to its constituents such as polysaccharide, organic acids, flavonoids, minerals, and other substances. In this study, wax apple polysaccharide (WAP) was isolated from this plant and its protective effect against ethyl carbamate (EC)|-induced oxidative damage was evaluated in human hepatocytes (L02 cells). Firstly, a series of analyses such as high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass spectrometry (GC/MS), and 1H and 13C nuclear magnetic resonance (NMR) were conducted to identify the structure of WAP. Thereafter, in vitro cell experiments were performed to verify the protective effects of WAP against EC-induced cytotoxicity, genotoxicity, and oxidative damage in L02 cells. Our results revealed that WAP is composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 2.20:|3.94:|4.45:|8.56:|8.86:|30.82:|39.78:|1.48. Using a combination of methylation and NMR spectroscopic analysis, the primary structure of WAP was identified as Araf-(1→, Glcp-(1→, →2)|-Araf-(1→, →3)|-Galp-(1→, →3)|-Araf-|(1→, and →6)|-Galp-|(1→. Cell experiments indicated that WAP exhibited significant protective effects on EC-treated L02 cells via suppressing cytotoxicity and genotoxicity, reducing reactive oxygen species (ROS) and O2•- formation, as well as improving mitochondrial membrane potential (MMP) and glutathione (GSH). In a nutshell, WAP has the potential as an important therapeutic agent or supplement for hepatic oxidative damage. Meanwhile, further studies are needed to prove the above effects in vivo at the biological and clinical levels.

Avocado peel extract loaded on chitosan nanoparticles alleviates urethane toxicity that causes lung cancer in a mouse model.

Lung cancer progresses without obvious symptoms and is detected in most patients at late stages, causing a high rate of mortality. Avocado peels (AVP) were thought to be biowaste, but they have antioxidant and anticancer properties in vitro. Chitosan nanoparticles (Cs-NPs) were loaded with various plant extracts, increasing their in vitro and in vivo anticancer activities. Our goal was to load AVP onto Cs-NPs and determine the role of AVP-extract or AVP-loaded Cs-NPs in controlling the progression of lung cancer caused by urethane toxicity. The AVP-loaded chitosan nano-combination (Cs@AVP NC) was synthesized and characterized. Our in vitro results show that Cs@AVP NC has higher anticancer activity than AVP against three human cancer cell lines. The in vivo study proved the activation of apoptosis in lung cancer cells with the Cs@AVP NC oral treatment more than the AVP treatment. Additionally, Cs@AVP NC-treated animals showed significantly higher p53 and Bax-expression levels and lower NF-κB p65 levels in their lung tissues than in positive control animals. In conclusion, our study demonstrated the superior anticancer potency of Cs@AVP NC over AVP extract and its ability to inhibit lung cancer proliferation. Therefore, oral consumption of Cs@AVP NC might be a promising treatment for lung cancer.

The effect of Moringa oleifera leaf extracts against urethane-induced lung cancer in rat model.

Lung cancer is one of the most common malignancies in the world, and chemotherapy can have unfavorable side effects. The aim of the present study is to evaluate the therapeutic anticancer role of Moringa oleifera leaf extracts (MLE) in urethane-induced lung cancer in adult male albino rats as compared to standard chemotherapy. Rats were categorized into four groups (10 rats/group), including negative control rats, urethane lung cancer model rats, MLE-treated lung cancer rats, and cisplatin-treated rats. Estimation of lung index, some biochemical markers of oxidative stress, quantitative real-time polymerase chain reaction (qRT-PCR), and histopathology and transmission electron microscopy were performed. The lung index was significantly increased about one-fold in urethane lung cancer model rats, but it decreased after MLE treatment. Also, MLE was able to improve the induced changes in glutathione, superoxide dismutase, and malondialdehyde concentration to be 3.8 ± 0.4 mg/g, 900.6 ± 58 U/g, and 172 ± 24 nmol/g, respectively. Additionally, after MLE treatment, the expression of EGFR-mRNA increased by about 50%. Our light and electron microscopic examination revealed that urethane group showed abnormally distributed excessive collagen fibers and the development of papillary adenocarcinoma from hyperplastic Clara cells in the lumen of terminal bronchiole with bronchiolar wall thickening, alveolar collapse, and inflammation. MLE group has moderate amount of collagen fiber and absence of tumor mass and provided more or less restoration of normal lung histology. Moreover, MLE was able to ameliorate the induced changes in mucin and PCNA positive cells in the lung by 10.8 ± 2.3%. Collectively, the current study showed that MLE could be used as anticancer agents alleviating changes associated with lung cancer in a urethane-induced lung cancer bearing rats thereby representing alternative options to toxic chemotherapy.

Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Wax apple (Syzygium samarangense) has received growing research interest for its high nutritional and medicinal value due to its constituents such as polysaccharide, organic acids, flavonoids, minerals, and other substances. In this study, wax apple polysaccharide (WAP) was isolated from this plant and its protective effect against ethyl carbamate (EC)‍-induced oxidative damage was evaluated in human hepatocytes (L02 cells). Firstly, a series of analyses such as high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass spectrometry (GC/MS), and 1H and 13C nuclear magnetic resonance (NMR) were conducted to identify the structure of WAP. Thereafter, in vitro cell experiments were performed to verify the protective effects of WAP against EC-induced cytotoxicity, genotoxicity, and oxidative damage in L02 cells. Our results revealed that WAP is composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 2.20:‍3.94:‍4.45:‍8.56:‍8.86:‍30.82:‍39.78:‍1.48. Using a combination of methylation and NMR spectroscopic analysis, the primary structure of WAP was identified as Araf-(1→, Glcp-(1→, →2)‍-Araf-(1→, →3)‍-Galp-(1→, →3)‍-Araf-‍(1→, and →6)‍-Galp-‍(1→. Cell experiments indicated that WAP exhibited significant protective effects on EC-treated L02 cells via suppressing cytotoxicity and genotoxicity, reducing reactive oxygen species (ROS) and O2•- formation, as well as improving mitochondrial membrane potential (MMP) and glutathione (GSH). In a nutshell, WAP has the potential as an important therapeutic agent or supplement for hepatic oxidative damage. Meanwhile, further studies are needed to prove the above effects in vivo at the biological and clinical levels.

Modelling mouse auditory response dynamics along a continuum of consciousness using a deep recurrent neural network.

Objective.Understanding neurophysiological changes that accompany transitions between anaesthetized and conscious states is a key objective of anesthesiology and consciousness science. This study aimed to characterize the dynamics of auditory-evoked potential morphology in mice along a continuum of consciousness.Approach.Epidural field potentials were recorded from above the primary auditory cortices of two groups of laboratory mice: urethane-anaesthetized (A,n= 14) and conscious (C,n= 17). Both groups received auditory stimulation in the form of a repeated pure-tone stimulus, before and after receiving 10 mg kg-1i.p. ketamine (AK and CK). Evoked responses were then ordered by ascending sample entropy into AK, A, CK, and C, considered to reflect physiological correlates of awareness. These data were used to train a recurrent neural network (RNN) with an input parameter encoding state. Model outputs were compared with grand-average event-related potential (ERP) waveforms. Subsequently, the state parameter was varied to simulate changes in the ERP that occur during transitions between states, and relationships with dominant peak amplitudes were quantified.Main results.The RNN synthesized output waveforms that were in close agreement with grand-average ERPs for each group (r2> 0.9,p< 0.0001). Varying the input state parameter generated model outputs reflecting changes in ERP morphology predicted to occur between states. Positive peak amplitudes within 25-50 ms, and negative peak amplitudes within 50-75 ms post-stimulus-onset, were found to display a sigmoidal characteristic during the transition from anaesthetized to conscious states. In contrast, negative peak amplitudes within 0-25 ms displayed greater linearity.Significance.This study demonstrates a method for modelling changes in ERP morphology that accompany transitions between states of consciousness using an RNN. In future studies, this approach may be applied to human data to support the clinical use of ERPs to predict transition to consciousness.

Self-Healable, Injectable Hydrogel with Enhanced Clotrimazole Solubilization as a Potential Therapeutic Platform for Gynecology.

Injectable, self-healing hydrogels with enhanced solubilization of hydrophobic drugs are urgently needed for antimicrobial intravaginal therapies. Here, we report the first hydrogel systems constructed of dynamic boronic esters cross-linking unimolecular micelles, which are a reservoir of antifungal hydrophobic drug molecules. The selective hydrophobization of hyperbranched polyglycidol with phenyl units in the core via ester or urethane bonds enabled the solubilization of clotrimazole, a water-insoluble drug of broad antifungal properties. The encapsulation efficiency of clotrimazole increases with the degree of the HbPGL core modification; however, the encapsulation is more favorable in the case of urethane derivatives. In addition, the rate of clotrimazole release was lower from HbPGL hydrophobized via urethane bonds than with ester linkages. In this work, we also revealed that the hydrophobization degree of HbPGL significantly influences the rheological properties of its hydrogels with poly(acrylamide-ran-2-acrylamidephenylboronic acid). The elastic strength of networks (GN) and the thermal stability of hydrogels increased along with the degree of HbPGL core hydrophobization. The degradation of the hydrogel constructed of the neat HbPGL was observed at approx. 40 °C, whereas the hydrogels constructed on HbPGL, where the monohydroxyl units were modified above 30 mol %, were stable above 50 °C. Moreover, the flow and self-healing ability of hydrogels were gradually decreased due to the reduced dynamics of macromolecules in the network as an effect of increased hydrophobicity. The changes in the rheological properties of hydrogels resulted from the engagement of phenyl units into the intermolecular hydrophobic interactions, which besides boronic esters constituted additional cross-links. This study demonstrates that the HbPGL core hydrophobized with phenyl units at 30 mol % degrees via urethane linkages is optimal in respect of the drug encapsulation efficiency and rheological properties including both self-healable and injectable behavior. This work is important because of a proper selection of a building component for the construction of a therapeutic hydrogel platform dedicated to the intravaginal delivery of hydrophobic drugs.

A new urea adducts method for PUFA concentration using green food grade solvents and avoiding ethyl carbamate formation.

This study aimed to selectively enrich stearidonic acid (SDA) together with γ-linolenic acid (GLA) in Echium plantagineum oil by urea complexation. The complexation process at room temperature was carried out replacing common organic solvents, such as hexane and ethanol, by alternative compounds, included in Green Solvent and Food Grade categories, adapting this process towards the principles of Green Chemistry. This substitution was also intended to avoid the generation of the toxic compound ethyl carbamate. Among all the solvents studied, the mixture propionic acid and α-pinene provided the best results, leading to a final product comprised of ∼99% of PUFA, with ∼45% SDA (∼14% in the original oil), and without apparition of ethyl carbamate. The procedure was tested on other raw materials (salmon and microalgae oils). The solvent was efficiently recuperated from the liquid phase (∼87% recovery) and reutilized once with almost identical results.

[Equol and its enantiomers inhibited urethane-induced lung cancer in mice].

OBJECTIVE: To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice. METHODS: A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison. RESULTS: A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups. CONCLUSION: Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

Introducing a flexible drug delivery system based on poly(glycerol sebacate)-urethane and its nanocomposite: potential application in the prevention and treatment of oral diseases.

In this study, a novel biopolymer based on poly(glycerol sebacic)-urethane (PGS-U) and its nanocomposites containing Cloisite@30B were synthesized by facile approach in which the crosslinking was created by aliphatic hexamethylene diisocyanate (HDI) at room temperature and 80 °C. Moreover, metronidazole and tetracycline drugs were selected as target drugs and loaded into PGSU based nanocomposites. A uniform and continuous microstructure with smooth surface is observed in the case of pristine PGS-U sample. The continuity of microstructure is observed in the case of all bionanocomposites. XRD result confirmed an intercalated morphology for PGSU containing 5 wt% of clay nanoparticles with a d-spacing 3.4 nm. The increment of nanoclay content up to 5%, the ultimate tensile stress and elastic modulus were obtained nearly 0.32 and 0.83 MPa, which the latter was more than eight-fold than that of pristine PGS-U. A sustained release for both dugs was observed by 200 h. The slowest and controlled drug release rate was determined in the case of PGSU containing 5 wt% clay and cured at 80 °C. A non-Fickian diffusion can be concluded in the case of tetracycline release via PGS-U/nanoclay bionanocomposites, while a Fickian process was detected in the case of metronidazole release by PGS-U/nanoclay bionanocomposites. As a result, the designed scaffold showed high flexibility, which makes it an appropriate option for utilization in the treatment of periodontal disease.

Equol and its enantiomers inhibited urethane-induced lung cancer in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice.@*METHODS@#A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison.@*RESULTS@#A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups.@*CONCLUSION@#Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

More evidence for a long-latency mismatch response in urethane-anaesthetised mice.

Long-latency mismatch responses to oddball stimuli have recently been observed from anaesthetised rodents. This electrophysiological activity is viewed through 200 to 700 ms post-stimulus; a window that is typically obstructed from analysis by the response to subsequent stimuli in the auditory paradigm. A novel difference waveform computation using two adjoining evoked responses has enabled visualisation of this activity over a longer window than previously available. In the present study, this technique was retroactively applied to data from 13 urethane-anaesthetised mice. Oddball paradigm waveforms were compared with those of a many-standards control sequence, confirming that oddball stimuli evoked long-latency potentials that did not arise from standard or control stimuli. Statistical tests were performed to identify regions of significant difference. Oddball-induced mismatch responses were found to display significantly greater long-latency potentials than identical stimuli presented in an equal-probability context. As such, it may be concluded that long-latency potentials were evoked by the oddball condition. How this feature of the anaesthetised rodent mismatch response relates to human mismatch negativity is unclear, although it may be tentatively linked to the human P3a component, which emerges downstream from mismatch negativity under certain conditions. These results demonstrate that the time dynamics of mismatch responses from anaesthetised rodents are more extensive than previously considered.

Novel therapeutic regimens for urethane-induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin-D3.

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Deviance detection in sound frequency in simple and complex sounds in urethane-anesthetized rats.

Mismatch negativity (MMN), which is an electrophysiological response demonstrated in humans and animals, reflects memory-based deviance detection in a series of sounds. However, only a few studies on rodents have used control conditions that were sufficient in eliminating confounding factors that could also explain differential responses to deviant sounds. Furthermore, it is unclear if change detection occurs similarly for sinusoidal and complex sounds. In this study, we investigated frequency change detection in urethane-anesthetized rats by recording local-field potentials from the dura above the auditory cortex. We studied change detection in sinusoidal and complex sounds in a series of experiments, controlling for sound frequency, probability, and pattern in a series of sounds. For sinusoidal sounds, the MMN controlled for frequency, adaptation, and pattern, was elicited at approximately 200 ms onset latency. For complex sounds, the MMN controlled for frequency and adaptation, was elicited at 60 ms onset latency. Sound frequency affected the differential responses. MMN amplitude was larger for the sinusoidal sounds than for the complex sounds. These findings indicate the importance of controlling for sound frequency and stimulus probabilities, which have not been fully controlled for in most previous animal and human studies. Future studies should confirm the preference for sinusoidal sounds over complex sounds in rats.

New function of polysaccharide from Rubus chingii Hu: protective effect against ethyl carbamate induced cytotoxicity.

BACKGROUND: Rubus chingii Hu is a widely cultivated fruit in China and has declared multiple bioactivities including antioxidative activity. Ethyl carbamate (EC), mostly found in fermented food and alcoholic beverages, is a recognized human carcinogen, and researchers have proposed the correlation between oxidative stress and its toxicity. This study acquired the polysaccharide from R. chingii (RP) and explored its effect on EC-induced cytotoxicity using Caco-2 cells as the cell model. RESULTS: Results showed that RP exhibited protection against EC-induced toxicity by repairing redox imbalance as indicative of mitigated mitochondrial membrane potential collapse, attenuated reactive oxygen species overproduction, and impeded glutathione depletion. Moreover, the structural features of RP were characterized and revealed that it was mainly constituted by galacturonic acid and arabinose, with an average molecular weight of 7.039 × 105 g mol-1 . CONCLUSION: Overall, our results provided a new approach dealing with the toxicity caused by EC from the perspective of oxidative stress and described a new potential healthy value of R. chingii Hu, which could contribute to the development of a promising dietary supplement and functional food. © 2020 Society of Chemical Industry.

Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice.

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1ß in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.

Application of bamboo leaves extract to Chinese yellow rice wine brewing for ethyl carbamate regulation and its mitigation mechanism.

Bamboo leaves extract (BLE) contains various effective ingredients, including phenolic compounds. In this study, the effect of BLE on ethyl carbamate (EC) formation was investigated in Chinese yellow rice wine brewing with three different fermentation starters (Saccharomyces cerevisiae, Saccharomyces cerevisiae and Lactobacillus brevis, and Chinese yeast). As a result, BLE showed significant inhibition effect on EC in multi-microbial fermented rice wine, by preventing the reactions between urea/citrulline and ethanol. We found that BLE had influence on arginine transport (GAP1, CAN1, ALP1, and VBA2 gene) in Saccharomyces cerevisiae (S. cerevisiae), which significantly up-regulated arginine uptake gene expression in vacuole (VBA2 gene) so that inhibited arginine metabolism. Besides, the presence of BLE could improve the overall quality of Chinese yellow rice wine. Consequently, it was worthwhile applying BLE to Chinese rice wine fermentation, especially the wine brewing with S. cerevisiae and Lactobacillus brevis starter.

Vegetable oil-based polyurethanes as antimicrobial wound dressings: in vitro and in vivo evaluation.

Preparation of efficient polyurethane-type wound dressings with tunable physicomechanical properties and widespread antimicrobial activity is considered in this work. A new type of soybean oil-based polyol with built-in urethane and quaternary ammonium groups is synthesized through a nonisocyanate route using carbonated soybean oil as an environmentally friendly, renewable resource-based raw material. Different formulations from this polyol and castor oil are prepared and converted to the polyurethane wound dressings via a reaction with isophorone diisocyanate. The dressing sample, with good cytocompatibility and efficient antimicrobial activity against various microbial strains, having tensile strength of 5 and 17 MPa at hydrated and dry state, elongation at the break of up to 400%, equilibrium water absorption and a water vapor transmission rate of 50% and 390 g m-2 day-1, is used for in vivo assay on a rat. Evaluation of the optimized dressing for a full-thickness non-sterilized wound has shown excellent progress of wound healing, since the tensile strength of regenerated skin reaches about 80% of normal healthy skin on day 21 after wounding. This has been significantly superior to the tensile strength of the regenerated skin of rats covered with non-antibacterial (∼50%) and cotton gauze (∼40%) dressings as blank and control groups.

Evodiamine suppresses Notch3 signaling in lung tumorigenesis via direct binding to γ-secretases.

BACKGROUND: Notch activation requires proteolytic cleavage of the receptor by γ-secretase protein complex. Inhibition of Notch receptor activation (e.g. Notch3) with γ-secretase inhibitor is a potential new therapeutic approach for the targeted therapy of non-small cell lung cancer (NSCLC). However, only a few safe and effective γ-secretase inhibitors have been discovered. Evodiamine (EVO), a compound derived from Euodiae Fructus (Chinese name, Wu-Zhu-Yu), exhibits remarkable anti-NSCLC activities. However, the underlying mechanisms of action have yet to be fully elucidated. PURPOSE: We sought to determine the involvement of Notch3 signaling in the anti-NSCLC effects of EVO, and to explore whether EVO suppressed Notch3 signaling by inhibiting γ-secretase in cultured A549 and H1299 NSCLC cells and in urethane-induced lung cancer FVB mouse model. METHODS: Cell viability, migration, stemness and cell cycle distribution of EVO were examined by the MTT assay, wound healing assay, soft agar colony assay and flow cytometry analysis, respectively. The binding affinity of EVO and γ-secretase complex was analyzed by molecular docking. Cellular thermal shift assay (CETSA) was performed to study the drug-target interactions in NSCLC cells. Protein levels were determined by Western blotting. RESULTS: EVO dramatically inhibited cell viability, induced G2/M cell cycle arrest, suppressed cell migration, and reduced stemness in NSCLC cells. Mechanistic studies indicated that EVO prevented the γ-secretase cleavage of Notch3 at the cell surface and hence inhibited Notch3 activation. Moreover, EVO notably reduced tumor growth in the mouse model and inhibited Notch3 activity in the tumors. CONCLUSION: This study provides new insights into the anti-NSCLC action of EVO, and suggests that suppressing Notch3 signaling by inhibiting γ-secretase is a mechanism of action underlying the anti-NSCLC effect of EVO.

New Insight on the Study of the Kinetic of Biobased Polyurethanes Synthesis Based on Oleo-Chemistry.

Nowadays, polyols are basic chemicals for the synthesis of a large range of polymers, such as polyurethane foams (PUF), which are produced with several other compounds, such as polyisocyanates. During the last decades, the oleo-chemistry has developed several routes from glycerides to polyols for the polyurethanes (PU) industry to replace mainly conventional fossil-based polyols. A large range of biobased polyols can be now obtained by epoxidation of the double bonds and ring-opening (RO) of the subsequent epoxides with different chemical moieties. In preliminary studies, the RO kinetics of an epoxidized model molecule (methyl oleate) with ethanol and acetic acid were investigated. Subsequently, polyols that were derived from unsaturated triglycerides were explored in the frame of e.g., PUF formulations. Different associations were studied with different mono-alcohols derived from epoxidized and ring-opened methyl oleate while using several ring-openers to model such systems and for comparison purposes. Kinetic studies were realized with the pseudo-first-order principle, meaning that hydroxyls are in large excess when compared to the isocyanate groups. The rate of isocyanate consumption was found to be dependent on the moiety located in ß-position of the reactive hydroxyl, following this specific order: tertiary amine >> ether > ester. The tertiary amine in ß-position of the hydroxyl tremendously increases the reactivity toward isocyanate. Consequently, a biobased reactive polyurethane catalyst was synthesized from unsaturated glycerides. These approaches offer new insights regarding the replacement of current catalysts often harmful, pungent, and volatile used in PU and PUF industry, in order to revisit this chemistry.

Sustained delivery of olanzapine from sunflower oil-based polyol-urethane nanoparticles synthesised through a cyclic carbonate ring-opening reaction.

The forefront horizon of biomedical investigations in recent decades is parcelling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring-opening reaction has been utilised to synthesise a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.