Effect of in vitro gastrointestinal digestion on the chemical composition and antioxidant properties of Ginkgo biloba leaves decoction and commercial capsules

In this study Ginkgo biloba leaves (GBL) decoction and commercial capsules were digested using an in vitro model. Thirty-six active compounds were identified and quantified by HPLC-ESI-MS analysis based on the MS/MS patterns (precursor ions and product ions) and retention times, in comparison with reference standards. Most compounds in GBL showed a significant decrease during intestinal digestion, with an exception of vanillic acid and biflavonoids. Bioaccessibility values of chemical compositions varied between decoction and capsules samples. Also, significant reductions of total flavonoids and total phenolic content was observed after in vitro digestion. Both, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity decreased after gastric digestion, but increased during intestinal digestion. Nevertheless, different behaviour was observed in reducing antioxidant power (FRAP) assay. Compared to the pH of digestion, the influence of digestive enzymes on the chemical composition and antioxidant activity of GBL was relatively minor. Overall, these results may help provide a valid foundation for further investigations on bioactive compounds and the pharmacodynamics of GBL

17β-Estradiol Enhances the Response of Plasmacytoid Dendritic Cell to CpG

Gender differences in immune capabilities suggest that sex hormones such as estrogens were involved in the regulation of the immunocompetence. Numerous studies also suggest that plasmacytoid dendritic cells (PDCs) play a pathogenic role in SLE. However, it is unclear whether estrogen can modulate the function of PDCs to influence the development of SLE. In the present study, PDCs from murine spleens were treated with 17β-estradiol (E2) and CpG respectively or both in vitro, then cell viability, costimulatory molecule expression, cytokine secretion of PDCs, as well as stimulatory capacity of PDCs to B cells were analyzed. Results showed that E2 and CpG increased the cell viability and costimulatory molecule expression on PDCs synergistically. Moreover, the intracellular and extracellular secretion of IFN-α was increased by E2 or E2 plus CpG. In addition, E2 and CpG also increased the stimulatory capacity of PDCs to B cells, and the viability of B cells was decreased after neutralizing IFN-α significantly. In the experiments in vivo, mice received daily s.c. injections of E2 and CpG respectively or both, then we found that the plasma concentration of IgM were elevated by E2 and CpG synergistically and the expression of IFN-α/β in spleens were noticeably increased by CpG plus E2 compared with the treatment of E2 or CpG only. This study indicates that E2 could exacerbate PDCs' activation with CpG, which further activates B cells to upregulate susceptibility to autoantigens. IFN-α plays an important role in the stimulatory effect of PDCs on B cells. E2 stimulation of IFN-α production may result in female prevalence in autoimmune diseases such as SLE through activation of PDCs. This study provides novel evidence of relationship between estrogen and SLE and also sheds light on gender biases among SLE patients

The effect of waste engine oil and waste polyethylene on UV aging resistance of asphalt.

Waste engine oil (WEO) and waste polyethylene (WPE) are two common wastes, which are easy to pollute the environment. As the primary material in road construction, natural asphalt is a non-renewable energy source and asphalt is vulnerable to ultraviolet (UV) radiation during the service life. It results in degradation of asphalt pavement performance. In this paper, 22 wt % to 82 wt % of WEO and WPE were used to modify asphalts and the UV aging simulation experiment was carried out. The physical parameters of asphalts before the UV aging experiment show that the asphalt containing 42 wt % WPE and 62 wt % WEO mixture (42 wt % WPE + 62 wt % WEO) has similar physical properties with that of the matrix asphalt. Besides, gel permeation chromatography (GPC) verifies that the molecular weight distribution of the asphalt containing 42 wt % WPE + 62 wt % WEO is close to that of the matrix asphalt. The storage stability test shows that 42 wt % WPE + 62 wt % WEO has good compatibility with the matrix asphalt. The functional groups and micro-morphology of asphalts before and after the UV aging experiment were investigated by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). FTIR results display that 42 wt % WPE + 62 wt % WEO can effectively reduce the formation of carbonyl and sulfoxide functional groups. AFM shows that 42 wt % WPE + 62 wt % WEO can also retard the formation of a bee-like structure in asphalt after the UV aging experiment. Based on the above results, it can be concluded that WEO and WPE mixture can replace part of asphalt and improve the UV aging resistance of asphalt

Microbial transformation of neomycin by a mutant of neomycin-producing Streptomyces fradiae

Utilizing a mutant of neomycin-producing Streptomyces fradiae mutagenized with neutron radiation, biotransformation of neomycin into modified compounds was studied. The biotransformation products were isolated by ion exchange chromatography and monitored by thin layer chromatography bioautography (TLCB). Antibacterial activity of biotransformation products against ten species of bacteria including four plant pathogens was tested qualitatively by TLCB and detected quantitatively by Oxford cup method. The minimal inhibitory concentration (MIC) of biotransformation products was tested by agar diffusion method. Three isolated transformation products had obvious antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris and Pseudomonas solanacarum. At the concentration of 50 μg/ml, the transformation product X had a similar antibacterial effect with neomycin but the transformation product Y and Z showed a decreased effect compared to neomycin except for P. vulgaris and P. solanacarum. However, the results from MIC analysis demonstrated that only the transformation product X maintained the same inhibitory effect with neomycin.Key words: Neomycin, biotransformation, Streptomyces fradiae, mutant, neutron radiation

The identities of insulin signaling pathway are affected by overexpression of Tau and its phosphorylation form

IntroductionHyperphosphorylated Tau formed neurofibrillary tangles was one of the major neuropathological hallmarks of Alzheimer’s disease (AD). Dysfunctional insulin signaling in brain is involved in AD. However, the effect of Tau pathology on brain insulin resistance remains unclear. This study explored the effects of overexpressing wild-type Tau (WTau) or Tau with pseudo-phosphorylation at AT8 residues (PTau) on the insulin signaling pathway (ISP).Methods293T cells or SY5Y cells overexpressing WTau or PTau were treated with or without insulin. The elements in ISP or the regulators of IPS were analyzed by immunoblotting, immunofluorescent staining and co-immunoprecipitation. Akt inhibitor MK2206 was used for evaluating the insulin signaling to downstream of mTOR in Tau overexpressing cells. The effects of anti-aging drug lonafarnib on ISP in WTau or PTau cells were also analyzed with immunoblotting. Considering lonafarnib is an inhibitor of FTase, the states of Rhes, one of FTase substrate in WTau or PTau cells were analyzed by drug affinity responsive target stability (DARTS) assay and the cellular thermal shift assay (CETSA).ResultsWTau or PTau overexpression in cells upregulated basal activity of elements in ISP in general. However, overexpression of WTau or PTau suppressed the ISP signaling transmission responses induced by insulin simulation, appearing relative higher response of IRS-1 phosphorylation at tyrosine 612 (IRS-1 p612) in upstream IPS, but a lower phosphorylation response of downstream IPS including mTOR, and its targets 4EPB1 and S6. This dysregulation of insulin evoked signaling transmission was more obvious in PTau cells. Suppressing Akt with MK2206 could compromise the levels of p-S6 and p-mTOR in WTau or PTau cells. Moreover, the changes of phosphatases detected in WTau and PTau cells may be related to ISP dysfunction. In addition, the effects of lonafarnib on the ISP in SY5Y cells with WTau and PTau overexpression were tested, which showed that lonafarnib treatment resulted in reducing the active levels of ISP elements in PTau cells but not in WTau cells. The differential effects are probably due to Tau phosphorylation modulating lonafarnib-induced alterations in Rhes, as revealed by DARTS assay.Conclusion and discussionOverexpression of Tau or Tau with pseudo-phosphorylation at AT8 residues could cause an upregulation of the basal/tonic ISP, but a suppression of insulin induced the phasic activation of ISP. This dysfunction of ISP was more obvious in cells overexpressing pseudo-phosphorylated Tau. These results implied that the dysfunction of ISP caused by Tau overexpression might impair the physiological fluctuation of neuronal functions in AD. The different effects of lonafarnib on ISP between WTau and PTau cells, indicating that Tau phosphorylation mediates an additional effect on ISP. This study provided a potential linkage of abnormal expression and phosphorylation of Tau to the ISP dysfunction in AD

Antioxidants and Antioxidant Capacity in Leafy, Stem, and Fruit Vegetables Including 50 Species

Epidemiological studies have confirmed that high intake of fruits and vegetables is associated with low incidence of many kinds of diseases, which are hypothesized to be owing to antioxidants in fruits and vegetables. In this study, three types (leafy, stem, fruit) vegetables including 50 species were systematically evaluated for their antioxidant capacity (AC) and antioxidants including total phenolic compound (TPC), total flavonoids (TF), and L-ascorbic acid (LAA). Results showed that vegetables types had no significant effects on antioxidants. Vegetables with vivid color like purple cabbage, purple dolichos lablab, purple cowpea, red pepper, yellow pepper, lotus root, and ginger ranked high in their antioxidants (TPC 32.76-117.63 mg gallic acid/g FW, TF 25.78-152.96 mg rutin/100g FW, LAA 69.11-165.44 mg/100g FW) and AC (FRAP 69.38-109.13 μmol Fe2+/100gFW, ABTS 2.19-3.75 μmol Trolox/gFW). Relatively, crown daisy, endive, celery stem, and cucumber had low antioxidants (TPC 2.66-6.29 mg gallic acid/g FW, TF 10.37-37.56 mg rutin/100g FW, LAA 14.64-39.44 mg/100g FW) and AC (FRAP 1.99-10.81 μmol Fe2+/100gFW, ABTS 0.39-0.68 μmol Trolox/gFW). TPC and LAA had strong positive correlations with AC regardless of vegetable types, while TF was positively related to AC only in leafy vegetables. The result would be valuable for both epidemiological research and dietary guidelines as these vegetables are affordable and widely available

Biological Function of Long Non-coding RNA (LncRNA) Xist

Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98–99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000–20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease