Povećanje stabilnosti i antioksidacijske aktivnosti antocijana iz ploda duda aciliranjem s jantarnom kiselinom

Research background. Anthocyanins possess valuable health-promoting activities with significant health benefits for humans. However, their instability is a limiting factor for their usage in functional foods and beverages. Experimental approach. In this work, a new method to enhance the stability of anthocyanins from mulberry fruit through acylation by using succinic acid as a selected acyl donor was explored. The Box-Behnken design of response surface methodology was applied to determine the optimized conditions for the acylation process. Results and conclusions. The highest acylation conversion rate was 79.04% at anthocyanins to succinic acid mass ratio 1:8.96, acylation duration 3 h and temperature 50 °C. Structural analysis of acylated anthocyanins revealed that succinic acid introduces a C-O-C bond and a hydroxyl group. The thermostability and light stability of mulberry anthocyanins were significantly improved after acylation, and the antioxidant activity expressed as total reducing power and Fe2+-chelating capacity of the acylated anthocyanins was also enhanced. Novelty and scientific contribution. Succinic acid acylation provides a novel method for stabilizing mulberry anthocyanins, as evidenced by the increased stability and antioxidant ability of anthocyanins, and thus facilitates its use in the food and nutraceutical industries.Pozadina istraživanja. Antocijani imaju pozitivni učinak na ljudsko zdravlje, no njihova im nestabilnost ograničava uporabu u proizvodnji funkcionalne hrane i pića. Eksperimentalni pristup. U ovom je radu ispitana nova metoda povećanja stabilnosti antocijana iz ploda duda aciliranjem s jantarnom kiselinom kao donorom acilne skupine. Optimalni uvjeti reakcije određeni su pomoću Box-Behnkenovog statističkog plana i metodom odzivnih površina. Rezultati i zaključci. Najveći postotak konverzije od 79,04 % postignut je pri masenom omjeru antocijana i jantarne kiseline od 1:8,96; trajanju acilacije od 3 h i temperaturi od 50 °C. Analizom strukture aciliranih antocijana utvrđeno je da sadržavaju C-O-C vezu i hidroksilnu skupinu iz jantarne kiseline. Aciliranje je bitno povećalo stabilnost antocijana pri izlaganju povišenim temperaturama i svjetlosti, te njihovu antioksidacijsku aktivnost, izraženu kroz ukupnu reducirajuću snagu i sposobnost keliranja Fe2+ iona. Novina i znanstveni doprinos. Aciliranje jantarnom kiselinom predstavlja novu metodu stabilizacije antocijana iz duda, što potvrđuje njihova povećana stabilnost i antioksidacijska sposobnost, čime je olakšana njihova primjena u proizvodnji hrane i nutraceutika

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

IntroductionBladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA.MethodsWe analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis.ResultsOur study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA.DiscussionOur study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy

Involvement of Autophagy in Cardiac Remodeling in Transgenic Mice with Cardiac Specific Over-Expression of Human Programmed Cell Death 5

Programmed cell death 5 (PDCD5) is a cytosolic protein suppressing growth of multiple types of cancer cells through activating p53. We hypothesized that PDCD5 plays an essential role in cardiac remodeling and function. PDCD5 was significantly up-regulated in the hearts from mice subjected to angiotensin II treatment or transverse aortic constriction. Thus, we generated transgenic mice over-expressing human PDCD5 under the control of alpha myosin heavy chain promoter to examine the role of PDCD5 in cardiac remodeling. Transgenic founder died spontaneously displayed enlarged heart. The high PDCD5 over-expressing line (10-fold) showed reduced survival rate, increase in heart weight normalized to body weight. Real-Time RT-PCR analysis revealed fetal gene program was up-regulated. Echocardiography and histopathological examination showed characteristics of dilated cardiomyopathy and heart failure in transgenic mice. Western blot and immunohistochemistry analysis showed autophagy was dramatically increased in transgenic mice as compared to WT littermates control mice, while apoptosis remained unchanged. The enhanced autophagy in high over-expressing line was associated with significant increase in p53 activity and its downstream target damage-regulated autophagy modulator expression. The low over-expressing line (3.5-fold) appeared normal, but was more susceptible to angiotensin II-induced cardiac hypertrophy. This study is the first providing evidence that PDCD5 plays an important role in cardiac remodeling

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs

Preparation and pH Controlled Release of Fe3O4/Anthocyanin Magnetic Biocomposites

Anthocyanins are a class of antioxidants extracted from plants, with a variety of biochemical and pharmacological properties. However, the wide and effective applications of anthocyanins have been limited by their relatively low stability and bioavailability. In order to expand the application of anthocyanins, Fe3O4/anthocyanin magnetic biocomposite was fabricated for the storage and release of anthocyanin in this work. The magnetic biocomposite of Fe3O4 magnetic nanoparticle-loaded anthocyanin was prepared through physical intermolecular adsorption or covalent cross-linking. Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and thermal analysis were used to characterize the biocomposite. In addition, the anthocyanin releasing experiments were performed. The optimized condition for the Fe3O4/anthocyanin magnetic biocomposite preparation was determined to be at 60 °C for 20 h in weak alkaline solution. The smooth surface of biocomposite from SEM suggested that anthocyanin was coated on the surface of the Fe3O4 particles successfully. The average size of the Fe3O4/anthocyanin magnetic biocomposite was about 222 nm. Under acidic conditions, the magnetic biocomposite solids could be repeatable released anthocyanin, with the same chemical structure as the anthocyanin before compounding. Therefore, anthocyanin can be effectively adsorbed and released by this magnetic biocomposite. Overall, this work shows that Fe3O4/anthocyanin magnetic biocomposite has great potential for future applications as a drug storage and delivery nanoplatform that is adaptable to medical, food and sensing

Library Screen for Inhibitors Targeting Norovirus Binding to Histo-Blood Group Antigen Receptors

Human noroviruses (NVs) are a common cause of nonbacterial gastroenteritis. The disease is difficult to control due to its widespread nature and the lack of antivirals or vaccines against NVs. The recent identification of human histo-blood group antigens (HBGAs) as NV receptors opens a new way for the discovery and design of antivirals against NVs. A saliva-based enzyme immune assay (EIA) was used to screen a synthetic-compound library for inhibition of the binding of norovirus-like particles to HBGA receptors. Among 5,000 compounds tested in the first round of screening, 153 compounds exhibited >50% inhibition of the binding of VA387 (an NV that binds to A, B, and H epitopes) to the A antigen in saliva at ∼50 μg/ml, and 14 of the 153 compounds revealed strong inhibition, with a 50% effective concentration of <15 μM. Ten and 11 of the 14 compounds also revealed inhibition of the binding of VA387 to the B and H antigens, respectively. Seven and 6 of the 14 compounds also blocked the binding of the prototype Norwalk virus (A and H binder) to the A and H antigens, respectively. One compound significantly inhibited the binding of MOH (A and B binder) to the A and B antigens, but no compound revealed any inhibitory effect on the binding of a Lewis binding strain (VA207) to the Lewis antigens. The EIA is a high-throughput method for large-scale library screening for antivirals against NVs. Studies to further characterize the lead compounds and to screen additional compounds for other NVs are ongoing in our laboratory

Empirical study with structural break on the relationship between financial development and economic growth of Jiangxi province

The empirical study over the period 1978-2011 found that the relationship between real per capita GDP and financial interrelation ratio structurally broke since 2004. From 1978 to 2003, economic growth and financial development had a long-term co-integration, and it showed one-way supply relationship according to the Granger causality test, which means the economic growth have a slowly leading function to the development of finance. From 2004 to 2011, the correlation between them became weaker and had no Granger causality, but there had a long-term co-integration and mutual causality relationship existed between loan and GDP during the whole period. From it we can see loan could boost output more persistently. Therefore, the enhanced economic power of Jiangxi province could promote further development of regional financial service industries, and we would propose some related policy suggestions in this paper