Bioinspired nanocatalytic tumor therapy by simultaneous reactive oxygen species generation enhancement and glutamine pathway-mediated glutathione depletion.

An insufficient intracellular H2O2 level and overexpressed glutathione (GSH) are still the major challenges for effective chemodynamic therapy (CDT). Inspired by the unique glutamine metabolism pathway in cancer cells, herein, intelligent nanocatalytic theranostics is used to enhance intracellular reactive oxygen species (ROS) accumulation via the production of H2O2 by a biomimetic nanozyme, and simultaneously reduce ROS consumption via the depression of GSH synthesis by the glutamine metabolic inhibitor. In this reactor, nano-sized Au and Fe3O4 coloaded dendritic mesoporous silica nanoparticles (DMSN-Au-Fe3O4) serve as the bifunctional nanozyme, where intracellular glucose is catalyzed into H2O2 by the glucose oxidase-mimicking Au nanoparticles and then immediately transformed into ˙OH by the peroxidase-like Fe3O4 nanoparticles. Then, CB839, the glutaminase (GLS) inhibitor, is grafted on the nanozyme, blocking the glutamine pathway and GSH biosynthesis. As a result, the as-designed nanoplatform with a three-pronged integration of Au-mediated H2O2 self-supply, Fe3O4-triggered Fenton-like reaction, and glutamine pathway-mediated GSH depletion significantly boosts the CDT efficacy, achieving remarkable and specific antitumor properties both in vitro and in vivo. This work not only paves a new way for rationally designing multi-functional nanozymes for achieving high therapeutic efficacy, but also provides new insights into the construction of bioinspired synergetic therapy by combining CDT and a key anticancer pathway.

Evidence-based core information for health communication of tobacco control: The effect of smoking on risks of female disease.

Objective: Cigarettes have become the the biggest killer of contemporary female's health and beauty. What kind of health information is suitable for the general public is an important issue to be discussed globally. The purpose of this study is to generate systematic, rigorous, public-demand-oriented and appropriate core information relevant to tobacco control based on the best available evidence, combined with audience preferences and pre-dissemination content review from multidisciplinary expertise in order to improve the effectiveness of health communication of tobacco control. Methods: Relevant systematic reviews meta-analysis that reported smoking on risks of female disease were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, and the International Clinical Trial Registry Platform. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was applied to assess the evidence in order to make rigorous core information. The audience prevalence survey was conducted to ensure that core information was targeted and tailored. Finally, the expert assessment was used for a pre-dissemination content review and to evaluate whether the core information was appropriate or not. Results: The final core information consisted of eight parts concerning the effects of smoking and female cardiovascular disease, diabetes, rheumatoid arthritis, respiratory disease, digestive system disease, mental disease, non-pregnant female reproductive system disease, as well as pregnant women and their fetuses. A total of 35 items of core information suitable for dissemination was included and the quality of evidence, the degree of public demand and the outcome of pre-dissemination content review were reported. Conclusion: The core information related to female cardiovascular system diseases, as well as liver cancer and upper gastrointestinal cancer is the preferred content for health communication of tobacco control. The quality of evidence for core information related to pregnant women and their infants, as well as diseases of reproductive system, respiratory system, and diabetes needs to be improved to meet high public demand. The core information related to mental disease is more suitable for dissemination to patients with mental illness than to the general public. Besides, dissemination of core information should be individualized. Evidence-based Core Information for Health Communication of Tobacco Control would be helpful to provide evidence support for health communication related to tobacco control and enhance public health literacy for international communities that have high smoking prevalence and related disease burden.

Ignored role of polyphenol in boosting reactive oxygen species generation for polyphenol/chemodynamic combination therapy.

Chemodynamic therapy (CDT) is a promising tumor-specific treatment, but still suffering insufficient reactive oxygen species (ROS) levels due to its limited efficacy of Fenton/Fenton-like reaction. Polyphenol, as a natural reductant, has been applied to promote the efficacy of Fenton/Fenton-like reactions; however, its intrinsic pro-apoptosis effects was ignored. Herein, a novel CDT/polyphenol-combined strategy was designed, based on Avenanthramide C-loaded dendritic mesoporous silica (DMSN)-Au/Fe3O4 nanoplatforms with folic acid modification for tumor-site targeting. For the first time, we showed that the nanocomplex (DMSNAF-AVC-FA) induced ROS production in the cytoplasm via Au/Fe3O4-mediated Fenton reactions and externally damaged the mitochondrial membrane; simultaneously, the resultant increased mitochondrial membrane permeability can facilitate the migration of AVC into mitochondrial, targeting the DDX3 pathway and impairing the electron transport chain (ETC) complexes, which significantly boosted the endogenous ROS levels inside the mitochondrial. Under the elevated oxidative stress level via both intra- and extra-mitochondrial ROS production, the maximum mitochondrial membrane permeability was achieved by up-regulation of Bax/Bcl-2, and thereby led to massive release of Cytochrome C and maximum tumor cell apoptosis via Caspase-3 pathway. As a result, the as-designed strategy achieved synergistic cytotoxicity to 4T1 tumor cells with the cell apoptosis rate of 99.12% in vitro and the tumor growth inhibition rate of 63.3% in vivo, while very minor cytotoxicity to normal cells with cell viability of 95.4%. This work evidenced that natural bioactive compounds are powerful for synergistically boosting ROS level, providing new insight for accelerating the clinical conversion progress of CDT with minimal side effects.

Knowledge, attitude and practices regarding health self-management among patients with osteogenesis imperfecta in China: an online cross-sectional survey.

OBJECTIVES: Assessing the knowledge, attitude and practices (KAP) regarding health self-management among patients with osteogenesis imperfecta (OI) in China. DESIGN: An online cross-sectional survey. SETTING: A structured questionnaire was distributed online through China-Dolls Center for Rare Disorders (CCRD), a non-governmental charity in China. PARTICIPANTS: Participants were all patients with OI from CCRD. After stratified sampling according to the economic level of residential city, 901 patients were proportionally selected and 869 patients completed the survey (response rate: 96.4%). MAIN OUTCOME MEASURES: Demographic characteristics and KAP information were gathered using a 5-point Likert scale. The score of each dimension of KAP was the sum of the scores of all included items. Χ2 test or Fisher's exact test was used to compare scores of different items. Ordinal regression was employed to determine the significant factors influencing KAP. RESULTS: A total of 802 questionnaires were included for analysis. Male respondents accounted for 57.1%, and 29.1% of respondents were of 26~30 years. More than half (50~60%) of patients knew the main symptoms of OI and the treatment of OI-related complications. Almost 80% of patients showed positive attitude. Nearly 60~70% of the patients were relatively able to take appropriate practice regarding OI management. There was a significant correlation between scores of knowledge and attitude, attitude and practice, as well as knowledge and practice. Patients aged 26~30 years, from urban areas and big cities, had higher KAP scores. Male patients showed better performance in knowledge, and highly educated patients perform better in practice. CONCLUSIONS: Patients with OI did not have sufficient knowledge on disease care and up-to-date caring guidelines, and their practice regarding health self-management also needs to be improved. Gender, age, educational level and economic level of residence can affect the level of KAP for patients, thus developing targeted and tailored programmes for patients with OI is highly recommended.

Degradation of aflatoxin B1 by a recombinant laccase from Trametes sp. C30 expressed in Saccharomyces cerevisiae: A mechanism assessment study in vitro and in vivo.

Aflatoxin B1 (AFB1) is the most harmful mycotoxin and presents risks to human health. Utilization of enzyme to degrade AFB1 is a promising strategy to overcome this problem. In this study, we evaluated the effect of recombinant laccase expressed in Saccharomyces cerevisiae on the degradation of AFB1. It was found that AFB1 could be degraded effectively by laccase up to 91%.The results of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) showed that there were four main degradation products of AFB1 including C16H22O4, C14H16N2O2, C7H12N6O and C24H30O6. Two possible degradation pathways were proposed: 1) AFB1 lost -CO continuously, and then double bonds of furan ring were broken after reactions with H2O, H+, and -NH2; 2) AFB1 occurred decarbonylation reaction after losing -CO and double bonds were broken by additional reaction with H+. Two toxicological activity sites in AFB1, including a double bond of furo-furan ring and lactone ring in the coumarin in moiety, were destroyed. The toxicity of AFB1 degradation products was evaluated on HepG2 cells and in vivo tests, and the results indicated a decrease in hepatocytes apoptosis, liver and kidney histopathological lesions, oxidative stress, and inflammation as compared to non-laccase degraded AFB1. Moreover, the AFB1 degradation products significantly decreased the cytotoxicity and hepatotoxicity. This investigation provides innovative evidence on the effectiveness of laccase expressed in Saccharomyces cerevisiae in detoxifying AFB1.

Molecular structure of different prepared pyrodextrins and the inhibitory effects on starch retrogradation.

Pyrodextrins with different molecular size were prepared by dry heating native corn starch with and without hydrochloric acid (HCl) at 180 °C for 0.5, 3, and 5 h. Those with HCl treatment displayed much smaller molecular size, narrower size distribution, and higher proportion of the chains with the degree of polymerization (DP) ~24-400 than the counterparts without HCl treatment. Pasting and rheological tests showed that the addition of pyrodextrins with HCl treatment displayed lower overall and setback viscosity, and reduced gel development and gel strength in comparison of those without HCl treatment. Differential scanning calorimetry (DSC) and wide-range X-ray (WXRD) data suggested that the pyrodextrin sample prepared by heating native starch with HCl at 180 °C for 5 h (A5) displayed the most effective inhibition on starch long-term retrogradation. This study could supply a pathway by applying pyrodextrins to both increase nutrition value and retard starch retrogradation for bakery and beverage industry.

Structural comparisons of pyrodextrins during thermal degradation process: The role of hydrochloric acid.

Hydrochloric acid (HCl) is widely used to prepare pyrodextrins, especially the water-soluble pyrodextrin. In this study, the structural difference between pyrodextrins as affected by HCl is compared by characterizing the molecular size, chain-length distributions (CLDs), crystallinity, and solubility. It is found that: 1) dry heating of starch granules without HCl mainly degrades long-amylose chains while slightly affects amylopectin branches; 2) the presence of HCl during dry heating decreases the degree of polymerization (DP) range of amylose chains upon degradation from DP ~ 833-1267 to DP ~ 206-432, suggesting that the presence of HCl accelerates the breakdown of long-amylose chains; 3) both pyroconversion processes have slight effects on A-(DP ~ 6-12) and B1- chains (DP ~ 12-24), which might explain the retained granular and crystalline structure during the process. This study could improve the understanding of the role of HCl in affecting the structure and property during pyroconversion of native starch.

Starch gelatinization in the surface layer of rice grains is crucial in reducing the stickiness of parboiled rice.

Parboiled rice has high nutritional value but unpleasant palatability. In this study, rice stickiness was significantly reduced by steaming during the parboiling process; however, continuing steaming past certain durations no longer affected rice stickiness. It was also found: (i) the degree of starch gelatinization (DSG) increases and starch crystallinity decreases with increasing steaming time; (ii) the molecular size and chain length distribution (CLD) of leached starch for both white and parboiled rice are significantly different from those of native starch; (iii) the relation between leached amylopectin amount and rice stickiness explains the reduced stickiness by parboiling; and (iv) starch gelatinization in the surface layer of rice grains during parboiling might be critically important in blocking starch leaching, consequently leading to a less sticky texture. This study supplies a way to manage glutinous rice stickiness by parboiling for the production of non-sticky rice foods.

Insights into maize starch degradation by high pressure homogenization treatment from molecular structure aspect.

High-pressure homogenization (HPH) is a common physical method used for starch modification. In this study, starch molecular structure in terms of chain-length distribution (CLD) and molecular size is characterized to explore the structural variations during HPH and its internal relations. It is found that: 1) the molecular size is significantly reduced by HPH treatments and further gradually decreases with HPH pressure increasing; 2) HPH degrades the long amylose chains with degree of polymerization (DP) ~ 2000-20,000 into short- and intermediate-amylose chains with DP ~ 100-1000 and DP ~ 1000-2000; 3) by HPH treatment, the proportion of amylopectin chains with DP ~ 6-12 and DP ~ 12-24 decreases while that with DP ~ 24-36 and DP ~ 36-100 increases, whereas, the amylopectin CLDs between HPH treated starch samples are not significantly varied; and 4) by a subtraction analysis, the molecular size of HPH treated starches shows a strong correlation with the proportion of degraded long amylose chains, indicating these long amylose chains might play a critical role in maintaining the large molecular size of starch. This study provides a further understanding of molecular features from the individual chains assembling into a whole branched molecule.

Molecular docking studies and in vitro degradation of four aflatoxins (AFB1 , AFB2 , AFG1 , and AFG2 ) by a recombinant laccase from Saccharomyces cerevisiae.

Here, molecular docking simulation was used to predict and compare interactions between a recombinant Trametes sp. C30 laccase from Saccharomyces cerevisiae and four aflatoxins (AFB1 , AFB2 , AFG1 , and AFG2 ) as well as their degradation at a molecular level. The computational result of docking simulation indicates that each of the aflatoxins tested can interact with laccase with a binding ability of AFB1 >AFG2 >AFG1 >AFB2 . Simultaneously, it also demonstrated that aflatoxin B1 ， B2 ， G1 ， G2 may interact near the T1 copper center of the enzyme through H-bonds and hydrophobic interactions with amino acid residues His481 and Asn288; His481； Asn288, and Asp230; His481 and Asn288. Biological degradation test was performed in vitro in the presence of a recombinant laccase. Degradation increased as incubation time increased from 12 to 60 hr and the maximum degradation obtained for AFB1 , AFB2 , AFG1 , and AFG2 was 90.33%, 74.23%, 85.24%, and 87.58%, respectively. Maximum degradation of aflatoxins was determined with a total activity 3 U laccase at 30 °C in 0.1 M phosphate buffer, pH 5.7 after 48-hr incubation. The experimental results are consistent with that of docking calculation on the biological degradation test of four aflatoxins by laccase. PRACTICAL APPLICATION: In this study, the degradation efficiencies of laccase for B and G series of aflatoxins were determined by computer simulation and verified by performing in vitro experiments. It can provide reference for rapid screening of aflatoxin degradation-related enzymes.

Effect of dry heating treatment on multi-levels of structure and physicochemical properties of maize starch: A thermodynamic study.

Dry heating treatment (DHT) is a common process widely used in food industry. In this study, the thermodynamic effects of DHT on starch structure and physicochemical properties are investigated. The results show that, with heating temperature increasing during DHT, the molecular size, long-amylose chains with degree of polymerization (DP) ~5000-20,000, and the crystallinity of maize starch are significantly reduced while the granular structure is retained with slightly aggregation between starch particles. The solubility of DHT starch increases from 0.5% to 2%, indicating the majority of DHT starch is still insoluble. DHT affects starch thermal property greatly that, it decreases the gelatinization enthalpy while increases the heterogeneity of starch crystallites. With heating temperature increasing, DHT reduces the overall viscosity of starch paste. The rheological property of DHT starch is frequency-dependent, showing the typical shear thinning behavior and "solid-like" gel property. Especially, as heating temperature reaches 190 °C, the shear resistance becomes stronger, and it is closer to Newtonian fluid. The results prove the thermodynamic effects of DHT on multi-levels of starch structure and physicochemical properties, also indicating the great potential to utilize DHT in modifying starch properties and amplifying its applications.

Insights into maize starch degradation by sulfuric acid from molecular structure changes.

In this study, the molecular structure of hydrolyzed maize starch by sulfuric acid is analyzed by characterizing the chain-length distribution (CLD) and molecular size. It is found that molecular size is dramatically reduced by acid hydrolysis for only 1 h while amylose content is gradually decreased from 28.3 % to 4.6 % with hydrolysis time prolonging. By quantifying the subtraction of CLDs between hydrolyzed sample and native starch, we find: 1) the long chains with degree of polymerization (DP)∼500-30000 of native starch are degraded by acid hydrolysis for only 1 h; 2) with hydrolysis time extending, the degradation of short-amylose chains and even short amylopectin chains are initialized; 3) molecular size of hydrolyzed starch shows a strong correlation with the parameters derived from the subtraction analysis. This study could help to further understand molecular features from the individual chain assembling to a fully branched molecule.

The increased stickiness of non-glutinous rice by alkali soaking and its molecular causes.

Non-glutinous rice is always less sticky than glutinous rice. By soaking two non-glutinous rice (Jingmi and Xianmi) with different concentrations of NaOH solution, the stickiness of cooked non-glutinous rice is significantly increased, which is closely associated with the removal of surface proteins of these treated rice grains. By investigating starch leaching characteristics and the molecular structure of leached starch, we find: (i) total solids and amylopectin amount in the leached materials increase by raising NaOH concentration; (ii) the molecular size and chain-length distributions (CLDs) of leached starch significantly differ between samples with different soaking treatments; (iii) a strong correlation between stickiness of cooked rice and total amount of leached amylopectin is established. (iv) molecular causes for the increased stickiness of alkali-soaked rice are put forward to explain the above observations. This study could broaden the applications of non-glutinous rice by altering its stickiness attribute with alkali soaking.