Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients’ cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.     

Intelligent system for visual web content analytics: A new approach and case study

The accuracy of searches for visual data elements, as well as other types of information, depends on the terms used by the user in the input query to retrieve the relevant results and to reduce the irrelevant ones. Most of the results that are returned are relevant to the query terms, but not to their meaning. For example, certain types of web contents hold hidden information that traditional search engines are unable to retrieve. Searching for the mathematical construct of 1/x using Google will not result in the retrieval of the documents that contain the mathematically equivalent expressions (i.e. x^?1). Because conventional search engines fall short of providing math-search capabilities. One of these capabilities is the ability of these search engines to detect the mathematical equivalence between users’ quires and math contents. In addition, users sometimes need to use slang terms, either to retrieve slang-based visual data (e.g. social media content) or because they do not know how to write using classical form. To solve such a problem, this paper proposed an AI-based system for analysing multilingual slang web contents so as to allow a user to retrieve web slang contents that are relevant to the user’s query. The proposed system presents an approach for visual data analytics, and it also enables users to analyse hundreds of potential search results/web pages by starting an informed friendly dialogue and presenting innovative answers.     

Constrained model predictive control for time-varying delay systems: Application to an active car suspension

This study investigates the problem of robust model predictive control (RMPC) for active suspension systems with time-varying delays and input constraints. The uncertainty is of convex polytopic type. Based on the Lyapunov-Krasovskii functional method, sufficient stability conditions of the time-varying delays systems are derived by linear matrix inequalities (LMIs) terms. At each time set, a feasible state feedback is obtained by minimizing an upper bound of the ‘worst-case’ quadratic objective function over an infinite horizon subject to constraints on inputs. Finally, a quarter-vehicle model is exploited to demonstrate the effectiveness of the proposed method.     

Elucidating the Interaction between Pyridoxine 5′-Phosphate Oxidase and Dopa Decarboxylase: Activation of B6-Dependent Enzyme

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, serves as a cofactor for scores of B6-dependent (PLP-dependent) enzymes involved in many cellular processes. One such B6 enzyme is dopa decarboxylase (DDC), which is required for the biosynthesis of key neurotransmitters, e.g., dopamine and serotonin. PLP-dependent enzymes are biosynthesized as apo-B6 enzymes and then converted to the catalytically active holo-B6 enzymes by Schiff base formation between the aldehyde of PLP and an active site lysine of the protein. In eukaryotes, PLP is made available to the B6 enzymes through the activity of the B6-salvage enzymes, pyridoxine 5′-phosphate oxidase (PNPO) and pyridoxal kinase (PLK). To minimize toxicity, the cell keeps the content of free PLP (unbound) very low through dephosphorylation and PLP feedback inhibition of PNPO and PLK. This has led to a proposed mechanism of complex formation between the B6-salvage enzymes and apo-B6 enzymes prior to the transfer of PLP, although such complexes are yet to be characterized at the atomic level, presumably due to their transient nature. A computational study, for the first time, was used to predict a likely PNPO and DDC complex, which suggested contact between the allosteric PLP tight-binding site on PNPO and the active site of DDC. Using isothermal calorimetry and/or surface plasmon resonance, we also show that PNPO binds both apoDDC and holoDDC with dissociation constants of 0.93 ± 0.07 μM and 2.59 ± 0.11 μM, respectively. Finally, in the presence of apoDDC, the tightly bound PLP on PNPO is transferred to apoDDC, resulting in the formation of about 35% holoDDC.     

Assessment of in vitro antioxidant, antibacterial and immune activation potentials of aqueous and ethanol extracts of Phyllanthus niruri

BACKGROUND: Recently much attention has been paid to biologically active plants because of their low production cost and fewer adverse effects compared with chemical drugs. In the present investigation the bioactivity of Phyllanthus niruri ethanol and aqueous extracts was evaluated in vitro. RESULTS: The ethanol extract of P. niruri showed a high level of flavonoid content (123.9 ± 0.002 mg g^?1), while the aqueous extract showed the highest 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH; IC₅₀6.85 ± 1.80 µmol L^?1) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS; 46.44 ± 0.53 µmol L^?1) free radical scavenging activities with high phenol content (376 ± 0.02 mg g^?1) and elevated levels of ferric reducing antioxidant power (FRAP; 23 883 ± 0.019 mmol g^?1) with excellent antibacterial activity against Staphylococcus aureus (20 mm inhibition zone) and Streptococcus agalactiae (12 mm inhibition zone), respectively, in addition to the best immune activation potential of human peripheral blood mononuclear cells (450.5%). CONCLUSIONS: It is clear from our results that both extracts of P. niruri has excellent bioactivity roles via elevated levels of antibacterial, antioxidant and percentage of peripheral blood mononuclear cell proliferation, which could lead to the development of medications for clinical use. Copyright © 2012 Society of Chemical Industry     

Antioxidant capacity and total phenolics of <Emphasis Type="Italic">Cyphostemma digitatum</Emphasis> before and after processing: use of different assays

In the framework of standardisation of new healthy food sources, this paper aimed to study the total phenolics and the antioxidant power of Cyphostemma digitatum (Vitaceae) in water and ethanol extracts, using 96-well micro plates with BMG FLUOstar Optima micro plate reader. Total phenolics by Folin–Ciocalteu method in the water extracts were significantly lower after processing, decreasing from 1.41 ± 0.06 g GAE/100 g in the raw leaves to 0.80 ± 0.08 g GAE/100 g in the processed sample; the ethanol extract revealed the same trend with higher values, decreasing from 1.95 ± 0.03 to 1.56 ± 0.12 g GAE/100 g. The antioxidant capacity was elucidated by four methods: TEAC, DPPH, FRAP and ORAC. No or very weak correlations were found between antioxidant assays and total phenolics; this confirms that the antioxidant capacity could be attributed to other molecules. The ORAC assay proved to be more powerful than the other assays; it showed 103.3 ± 2.5 mmol/100 g Trolox equivalents in the raw leaves ethanol extract and 91.9 ± 3.0 mmol/100 g in the processed sample. ORAC assay showed the opposite for the water extract where the antioxidant capacity increased from 16.7 ± 0.2 to 41.7 ± 2.7 mmol/100 g Trolox equivalents after processing, which could be attributed to new water-soluble compounds generated in the consumed form.     

Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the ¹H NMR, ¹³C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.     

Three-level designs: Evaluation and comparison for screening purposes

Since their introduction by Box and Hunter, resolution criteria have been widely used when comparing regular fractional factorials designs. In this article, we investigate how a generalized resolution criterion can be used to assess some recently developed three-level screening designs, such as definitive screening designs (DSDs) and screening designs from weighing matrices. The aim of this paper is to capture the projection properties of those three-level screening designs, complementing the work of Deng and Tang, who used generalized resolution and minimum aberration criteria for ranking different two-level designs, particularly Plackett-Burman and other nonregular factorial designs. An advantage of generalized resolution, extended here to work on three-level designs, is that it offers a useful criterion for ranking three-level screening designs, whereas the Deng and Tang resolution is used mainly for the assessment of two-level designs. In addition, we applied a projection estimation capacity (PEC) criterion to select three-level screening designs with desirable properties. Practical examples and the best projections of the designs are presented in tables.     

Study of the impact of a new hurdle technology composed of electro‐activated solution and low heat treatment on the canned pea and corn quality and microbial safety

The objective of this work was to evaluate the quality of sterilised canned pea and corn in electro‐activated brine solutions at moderate temperatures. The lowest change in vitamin C was associated with the lowest heat treatment, while the short treatment time resulted in significant changes in texture and colour of vegetables. Best texture profile was obtained with the acid electro‐activated brine solution for pea and corn. The neutral electro‐activated brine solution resulted in a less firm texture for pea and corn. The green colour and brightness of canned pea were higher when neutral solution was used (a* = ?8.4 ± 0.3) than for the acidic one (a* = ?3.7 ± 0.6). The yellowness of corn was better with the neutral electro‐activated brine solution (b* = 36.32 ± 1.24) than with the acidic one (b* = 28.44 ± 2.39). Thirty‐three percent decrease of energy consumption was obtained using the electro‐activation technology.