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Inflammation prompts cancer development and promotes all stages of tumorigenesis. Calcitriol is a nutraceutical essential regulator for host health benefits. However, the influence of calcitriol on inflammatory mediators involved in cancer cells is not clear. This study aimed to assess the sensitivity of calcitriol alone and combined with capric acid, and identify the possible influence of calcitriol on inflammatory mediators. The colorectal cancer cell line (HCT116) was induced by LPS/TNF-α and the inflammation and metastatic mediators (IL-1β, IL-6, IL-17) were quantified in calcitriol and capric acid supplemented colon cancer cells. The mRNA and protein expression of MMP-2, NF-κB and COX-2 were quantified. The significant reduction in MMP-2 expression was confirmed at combination treatment by zymogram analysis. Our findings demonstrated the anti-inflammatory and anti-metastatic potentials of capric acid and calcitriol in individual exposure in a combination of human colon cancer cell lines (HCT116). These abilities may be due to the inhibition of COX-2 mediators and NF-κB transcription factor and reciprocally regulated MMP-2 and MMP-9 signaling pathways. These findings elucidate the activation of COX-2 and NF-κB via disruption of the cellular outer matrix could be considered a novel molecular target suitable for colorectal cancer therapy. This study confirmed that capric acid activates calcitriol sensitization in colon cancer cells and could be used as a successful supplement for intestinal diseases and colon aberrations. [ABSTRACT FROM AUTHOR]

A solvothermal technique was used to prepare a Zn–benzenetricarboxylic acid (Zn@BTC) organic framework covered with a carboxymethyl cellulose (CMC/Zn@BTC). Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), and Brunauer, Emmett, and Teller (BET) surface area were applied to characterize CMC/Zn@BTC. Moreover, the anticancer, anti-migrative, anti-invasive, and anti-proliferative action of CMC/Zn@BTC nanoparticles were assessed on cancer cell lines. Apoptotic markers and DNA damage were assessed to explore the cellular and biological changes induced by CMC/Zn@BTC nanoparticles. The microscopic observation revealed that CMC controls the surface morphology and surface characteristics of the Zn@BTC. The obtained BET data revealed that the Zn@BTC nanocomposite surface area lowers from 1061 m2/g to 740 m2/g, and the pore volume decreases from 0.50 cm3/g to 0.37 cm3/g when CMC is applied to Zn@BTC nanocomposites. The cellular growth of DLD1 and A549 was suppressed by CMC/Zn@BTC, with IC50 values of 19.1 and 23.1 μg/mL, respectively. P53 expression was upregulated, and Bcl-2 expression was downregulated by CMC/Zn@BTC, which promoted the apoptotic process. Furthermore, CMC/Zn@BTC caused DNA damage in both cancer cell lines with diverse impact, 66 percent (A549) and 20 percent (DLD1) compared to cisplatin's 52 percent reduction. CMC/Zn@BTC has anti-invasive properties and significantly reduced cellular migration. Moreover, CMC/Zn@BTC aims key proteins associated with metastasis, proliferation and programmed cellular death. [ABSTRACT FROM AUTHOR]

Abstract A series of thirteen new aryl/hetarylbichalcophene-5-carboxamidines was prepared and screened for an in vitro anti-proliferative activity against sixty cancer cell lines. The tested monocationic bichalcophenes displayed promising potent anticancer activity against most cancer cell lines with GI 50 values of 1.34–3.09 μM. The most potent compound was derivative 8 (median GI 50 and TGI values of 1.34 and 3.23 μM, respectively), being also the least cytotoxic in this bichalcophene series with an LC 50 of 77.6 μM. The most responsive cancer cell lines were leukemia (SR and K-562) and colon (HCT-15 and HT29) with GI 50 in the sub-micromolar range. The effect of the tested bichalcophenes on normal human lung fibroblast (WI-38) cell line showed that they exerted their antiproliferative activity outside the realms of causing any toxicity in normal cells. To study apoptotic profiles of representatives of this class, compounds 4h , 4i , and 8 were found to cause significant reductions in cdk1 expression in HCT-116 colon cells by 46, 79, and 84%, respectively versus 52% reduction by 5- Flourouracil (5-FU). These three compounds were also unique being the only derivatives that significantly elevated the expression of p53 by ∼2, 4, and 5 folds, respectively. The tested bichalcophenes exhibited moderate to potent antioxidant activity in DPPH and ABTS as well as hydroxyl radical scavenging assays. Moreover, compounds IIIb , IIIc , 4c , and 4i , showed the highest pro-oxidant activity. Finally, to aid future endeavors for optimization of this series, a 5 descriptor 2D-QSAR model was derived from the common physicochemical parameters of these bichalcophenes and the external validation proved the model's good predictive efficiency. Graphical abstract Image 1 Highlights • A new series of aryl/hetarylbichalcophene-5-carboxamidines was prepared. • The new monoamidines displayed potent anti-proliferative activity. • The most potent and least cytotoxic compound was isoquinoline derivative 8. • The most responsive cancer cell lines were leukemia SR and K-562. • Most of the tested monoamidines exhibited significant selectivity index. [ABSTRACT FROM AUTHOR]

The cyclic voltammetry technique was used to study the electrochemical behavior of vanadyl sulfate in absence and presence of antibiotic (cefazolin) in 0.1 M KCl under different pH values at 300.15 K. The redox behavior of vanadyl sulfate has been studied by using glassy carbon electrode, Ag/AgCl as a reference electrode and Pt wire as a counter electrode under potential from +1500 mV to −1000 mV. One anodic peak and one cathodic peak are observed in cyclic voltammograms. Peak current ratio and peak potential separation (ΔE) was calculated, the higher values of them gave an indication about systems under study are quasi-reversible. The effect of pH, scan rate and concentration of electroactive species on the interaction between vanadyl sulfate and antibiotic were studied. Charge transfer coefficients (α), the heterogeneous electron transfer rate constants (k s ) and the diffusion coefficients (D) involved in the redox reaction were evaluated. [ABSTRACT FROM AUTHOR]

Four previously undescribed sucrose diester of aryldihydronaphthalene-type lignans, named echiumins A-D, were isolated from the butanol fraction of Echium angustifolium Mill, in addition to a known compound, trigonotin A, which is reported for the first time from the title plant. The structures of isolated compounds were elucidated using spectroscopic methods such as HRESIMS and 1D and 2D NMR spectroscopy. The isolated compounds displayed strong to weak antitumor activity against HepG2 and MCF7 cancer cell lines, with echiumins A and D showed the most potent activity. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) were synthesised with hydrothermal autoclaving technique by using AgNO3 salt (silver precursor) at different concentrations (0.01, 0.1, 0.55, 1.1, 5.5, and 11 mM) and porcine skin (1% (w/v) ) gelatin polymeric matrix (reducing and stabiliser agent). The reaction was performed in an autoclave at 103 kPa and 121°C and the hydrothermal autoclaving exposure time and AgNO3 molar concentration were varied at a constant porcine skin gelatin concentration. The asprepared AgNPs were characterised by UV-visible spectroscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The antibacterial properties of AgNPs were tested against gram-positive and gram-negative bacteria. Furthermore, 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide and 2,2-diphenyl-1-picrylhydrazyl assays were used to test whether the synthesised AgNPs can be potentially applied in cancer therapy or used as an antioxidant. This approach is a promising simple route for synthesising AgNPs with a smaller average particle 10 nm diameter. Furthermore, AgNPs exhibited a good cytotoxicity activity, reducing the viability of the liver cancer cell line HepG2 with a moderate IC50; they also showed a low-to-fair antioxidant activity. In addition, AgNPs had a remarkable preferential antibacterial activity against gram-positive bacteria than gram-negative bacteria. Therefore, these fabricated AgNPs can be used as an antibacterial agent in curative and preventive health care. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) were synthesised with hydrothermal autoclaving technique by using AgNO3 salt (silver precursor) at different concentrations (0.01, 0.1, 0.55, 1.1, 5.5, and 11 mM) and porcine skin (1% (w/v)) gelatin polymeric matrix (reducing and stabiliser agent). The reaction was performed in an autoclave at 103 kPa and 121°C and the hydrothermal autoclaving exposure time and AgNO3 molar concentration were varied at a constant porcine skin gelatin concentration. The as‐prepared AgNPs were characterised by UV–visible spectroscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The antibacterial properties of AgNPs were tested against gram‐positive and gram‐negative bacteria. Furthermore, 3‐(4,5‐dimethylthiazol‐2‐yl) 2,5‐diphenyltetrazolium bromide and 2,2‐diphenyl‐1‐picrylhydrazyl assays were used to test whether the synthesised AgNPs can be potentially applied in cancer therapy or used as an antioxidant. This approach is a promising simple route for synthesising AgNPs with a smaller average particle 10 nm diameter. Furthermore, AgNPs exhibited a good cytotoxicity activity, reducing the viability of the liver cancer cell line HepG2 with a moderate IC50; they also showed a low‐to‐fair antioxidant activity. In addition, AgNPs had a remarkable preferential antibacterial activity against gram‐positive bacteria than gram‐negative bacteria. Therefore, these fabricated AgNPs can be used as an antibacterial agent in curative and preventive health care. [ABSTRACT FROM AUTHOR]

An Anton Par Model 55 densimeter was used to measure the densities of copper sulphate solutions in H 2 O and EtOH–H 2 O at 298.15 K, 303.15 K, 308.15 K, and 313.15 K. The acquired information was used to ascertain the apparent molar volumes, limiting partial molar volumes, and transfer partial molar volumes of copper sulphate. These computed parameters were utilized to decipher the solute–solute and solute–solvent interactions of copper sulphate in an aqueous ethanol solution. The ion solvation behavior of copper sulphate in water and aqueous ethanol over the range of 298.15–313.15 K was studied using the electrical conductivity principle. The Kraus–Bray and Shedlovsky models of conductivity were used to analyze the obtained conductance data. From the obtained data, the limiting molar conductance λ ° m , association constant K A , energy of activation of the rating process ( E a ), and related thermodynamic parameters were determined. The Walden product ( λ ° m η 0 ) was determined. The standard thermodynamic parameters of association (Δ G ° A , Δ H ° A ) were calculated and discussed. Increased ion–solvent and solvent–solvent interactions are indicated by limiting molar conductance values with an increasing amount of ethanol. The negative Δ G ° A values indicate that the association processes in all of the studied systems are spontaneous processes. The negative estimation of (Δ H ° A ) demonstrates that the association processes is exothermic in nature. [ABSTRACT FROM AUTHOR]

Novel tetrazole-based diselenides and selenoquinones were synthesized via azido-Ugi and sequential nucleophilic substitution (S N ) strategy. Molecular docking study into mammalian TrxR1 was used to predict the anticancer potential of the newly synthesized compounds. The cytotoxic activity of the compounds was evaluated using hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cancer cells and compared with their cytotoxicity in normal fibroblast (WI-38) cells. The corresponding redox properties of the synthesized compounds were assessed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), glutathione peroxidase (GPx)-like activity and bleomycin dependent DNA damage. In general, diselenides showed preferential cytotoxicity to HepG2 compared to MCF-7 cells. These compounds exhibited also good GPx catalytic activity compared to ebselen (up to 5 fold). Selenoquinones 18 , 21 , 22 and 23 were selected to monitor the expression levels of caspase-8, Bcl-2 and Ki-67 molecular biomarkers. Interestingly, these compounds downregulated the Bcl-2 and Ki-67 expression levels and activated the expression of caspase-8 in HepG2 cells compared to untreated cells. These results indicate that some of the newly synthesized compounds possess anti-HepG2 activity. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans ( C. albicans ) fungus as well as against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure–activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations. [ABSTRACT FROM AUTHOR]

A new series of Cu2+, Pt4+, Pd2+, Au3+ and Nd3+ complexes derived from 2-(pyridin-1-ium-1-yl) acetate have been synthesized and characterized using elemental analyses, spectral (infrared (IR), UV-visible, mass, 13C NMR and 1H NMR), magnetic and thermal measurements. IR results suggest that the ligand acts in a neutral monodentate fashion in all complexes. Octahedral geometry is proposed for Cu2+ and Pt4+ complexes and square-planar for Pd2+ and Au3+ complexes. The bond lengths, bond angles, and HOMO and LUMO were calculated. Superoxide dismutase-like radical scavenger activity and cytotoxic activity of the isolated complexes on HepG2 liver cancer cells have been screened. Ligand and complexes (Pt4+ and Nd3+) exhibit potent antioxidant activity upon coordination while Cu2+ and Au3+ complexes do not show superoxide dismutase-like radical scavenger activity. The cytotoxic activity assay against HepG2 cell line proves that the ligand and its Pt4+ complex have a high cytotoxic activity, while the other complexes showed no cytotoxic activity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be also described for each drug. [ABSTRACT FROM AUTHOR]

A biologically active agent based on a Zn-1,3,5-benzen tricarboxylic acid (Zn-BTC) framework incorporated into a chitosan (CS) biopolymer (Zn-BTC@CS) was successfully synthesized using a microwave irradiation technique. The synthesized Zn-BTC@CS was characterized using a scanning electron microscope (SEM) and the obtained data indicated a highly smooth surface morphology of the synthesized Zn-BTC and no morphological changes when the Zn-BTC covered the CS. In addition, the particle size diameter varied from 20 to 40 nm. XRD displayed a well-maintained Zn-BTC structure, and the crystal structure of Zn-BTC was not distorted by the composition of Zn-BTC and chitosan in the nanocomposite. Data from BET analysis revealed that the specific surface area of the Zn-BTC was reduced from 995.15 m2/g to 15.16 m2/g after coating with chitosan. The pore size distribution and pore volume of the Zn-BTC, Zn-BTC@CS were centered at 37.26 nm and at 22.5 nm, respectively. Zn-BTC@CS exhibited anticancer efficacy against lung and colon cancer cell lines. Zn-BTC@CS inhibited the proliferation of A549 and DLD-1 cancer cell lines in a dose-dependent manner with IC50 values of 13.2 and 19.8 µg/mL for the colon and lung cancer cell lines, respectively. Zn-BTC@CS stimulated the apoptotic process through up-regulating P53 expression and down-regulating Bcl-2 expression. Moreover, Zn-BTC@CS induced in vitro DNA fragmentation in both cancer cell lines with significantly different affinity by 66% (A549) and 20% (DLD-1) versus 52% reduction by Cisplatin. Zn-BTC@CS (IC50) exhibited anti-invasive activity and dramatically inhibited the migration of lung and colon cancer cell lines. This study provides evidence that Zn-BTC@CS targets the essential proteins involved in proliferation, metastasis, and apoptosis. Thus, Zn-BTC@CS has chemotherapeutic potential for inhibiting lung and colon cancer viability and growth. [ABSTRACT FROM AUTHOR]

[Display omitted] • Co2+-, Ni2+-, and Cu2+-complexes of quinxalyl hydrazone derivative are synthesized and characterized. • The antimicrobial (bacteria and fungi) and anticancer potential of Co–, Ni-, and Cu-complexes and their ligand are examined. • Their binding to ct DNA is examined via UV–Visible spectroscopy and hydrodynamic measurements. • Co–, Ni, and Cu-complexes exhibited more biological reactivity over their free ligand based on Tweedy's chelation theory. With the facile condensed carbonyl gourp of 2-hydorxybenzaldehyde with the amino group of quinoxalyl-2-carbohydrazide, a new chelating quinoxalyl hydrazone derivative ligand (H 2 Lpx) was constructed. Its coordination behavior towards three divalent Co2+, Ni2+, and Cu2+ ions was discovered by building up three new metallo-organic complexes (CoLpx, NiLpx, and CuLpx, respectively). Confirmation of their chemical structure was formulated by applying different spectroscopic methods, as well as, the micro-elemental (C,H,N) and thermogravimetric analyses, the conductance, and magnetic evaluations. The inhibition behavior of the free ligand and its metallo-organic complexes against the cell growth of six entitled microorganisms (three fungal and three bacterial types) and three tumors of humans was estimated considering the effective role of the divalent metal ions (Co2+, Ni2+, and Cu2+ ions in their metallo-organic complexes). The interacting nature of H 2 Lpx, CoLpx, NiLpx, and CuLpx, with calf thymus DNA (ct DNA) was manifested within the viscometric, spectrophotometric titrations and gel electrophoresis. The three complexes (CoLpx, NiLpx, and CuLpx) exposed a respectable inhibition attitude more than that of H 2 Lpx depending on the inhibition zone areas of the microbial series growth in mm and the half-inhibition concentration in µM (IC 50) for the tumor cell lines' growth. Establishing of the interacted modes between H 2 Lpx and MLpx with ct DNA was built upon the shifts of the spectral scans for their solutions. In addition, chromism type, Gibb's free energy, and binding constant values (Δ G b ≠ and K b , respectively) helped to distinguish their interacted modes, which supported DNA damage. The bio-action of MLpx complexes was highly modified compared to that of H 2 Lpx towards ct DNA. [ABSTRACT FROM AUTHOR]

Glutathione is a natural tripeptide that plays a major role in different physiological processes in the human body. Determination of glutathione in different body fluids and tissues is essential for early diagnosis and follow-up of various diseases. The assay of glutathione is problematic because of the high polarity, the limited stability, and the aliphatic structure, which lacks the appropriate chromophore for UV detection. A number of methods have been reported for determination of glutathione using different techniques. High-performance liquid chromatography was employed in both reverse phase and hydrophilic interaction modes. Electrochemical methods exploited the redox activity of glutathione to allow for quantification by different electrodes after chemical modification, including glassy carbon, carbon paste, and nanocomposite electrodes. Capillary zone electrophoresis was used with less need for derivatization which makes it simpler, faster, and more economic. A number of nanosensors and probes have been developed to assay glutathione in biological fluids using semiconductor nanoparticles, quantum dots, genetically engineered green fluorescent probes, and new derivatives of known dye classes. This work is an updated review of the methods of analysis of glutathione and glutathione disulfide in pharmaceuticals and biological fluids with more emphasis on the technical problems and the assay artifacts. [ABSTRACT FROM AUTHOR]

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c , naphthoquinone 5 , and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities. Image 1 • Nineteen organoselenides were synthesized. • Cytotoxicity was evaluated in HepG2 and MCF-7 cell lines. • Selective cytotoxicity was estimated using normal WI-38 cells. • Compounds modulated the expression of Bcl-2, IL-2, IL-6 and CD40 in HepG2 cells. • Redox profiles were estimated employing ABTS, DPPH, and GPx-like activity assays. [ABSTRACT FROM AUTHOR]

Emerging research findings have shown that a centrosomal protein (CEP55) is a potential oncogene in numerous human malignancies. Nevertheless, no pan-cancer analysis has been conducted to investigate the various aspects and behavior of this oncogene in different human cancerous tissues. Numerous databases were investigated to conduct a detailed analysis of CEP55. Initially, we evaluated the expression of CEP55 in several types of cancers and attempted to find the correlation between that and the stage of the examined malignancies. Then, we conducted a survival analysis to determine the relationship between CEP55 overexpression in malignancies and the patient's survival. Furthermore, we examined the genetic alteration forms and the methylation status of this oncogene. Additionally, the interference of CEP55 expression with immune cell infiltration, the response to various chemotherapeutic agents, and the putative molecular mechanism of CEP55 in tumorigenesis were investigated. The current study found that CEP55 was upregulated in cancerous tissues versus normal controls where this upregulation was correlated with a poor prognosis in multiple forms of human cancers. Additionally, it influenced the level of different immune cell infiltration and several chemokines levels in the tumor microenvironment in addition to the response to several antitumor drugs. Herein, we provide an in-depth understanding of the oncogenic activities of CEP55, identifying it as a possible predictive marker as well as a specific target for developing anticancer therapies. [ABSTRACT FROM AUTHOR]

The structures and thermodynamic parameters of hydrated lithium ion clusters incorporating a single lithium ion and up to six water molecules have been determined with density functional (DFT) and Hartree-Fock (HF) at the RB3LYP/631G(d,p) levels of theory. The possible formed structures are found to be 23 Li + (H 2 O) n complex for n = 1–6. The primary solvation shell in the gas phase is confirmed to be tetrahydrated in aqueous environment. Very important role of intermolecular hydrogen bond in determining the stability of solvation process of different ions is confirmed by theoretical studies. The calculated gas phase coordination number in the first solvation sphere of a hydrated lithium metal ion is found to be four and the same is also confirmed by the experimental findings. The equilibrium lithium–oxygen distance of 1.970 Å at the present B3LYP level of study is in excellent agreement with the X-ray diffraction result of 1.980 Å and neutron scattering study with a result of 1.90 Å for a tetrahydrated lithium cluster. NBO was analyzed and discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a leading cause of death worldwide and continuous efforts are exerted to develop novel biomarkers and therapeutic agents that could help in early diagnosis and treatment. Analysis of a pan-cancer model that includes a list of human tumors could provide us with a global solution to the heterogeneous condition of human cancers. One of the basic approaches for the detection of potential tumor biomarkers and drug targets is the assessment of specific proteins that show upregulation in cancerous tissues versus normal ones. We showed that ECT2 could be considered as a prognostic and immunological biomarker in a list of human cancers through the investigation of several databases. We also employed a chemoinformatics approach to analyze potential inhibitors for ECT2 that could finally act as antitumor agents. Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs. [ABSTRACT FROM AUTHOR]

Oilseeds of the plant family Brassicaceae are important for providing both lipid and protein contents to human nutrition. Cruciferins (12S globulins) are seed storage proteins, which are getting attention due to their allergenic and pathogenicity related nature. This study describes the purification and characterization of a trimeric (∼190 kDa) cruciferin protein from the seeds of Brassica nigra (L.). Cruciferin was first partially purified by ammonium sulfate precipitation (30% saturation constant) and further purified by size exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82% sequence homology with cruciferin from Arabidopsis thaliana . The 50–55 kDa monomeric cruciferin produced multiple bands of two major molecular weight ranges (α-polypeptides of 28–32 kDa and β-polypeptides of 17–20 kDa) under reduced conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further separation of the bands into their isoforms with major pI ranges between 5.7 and 8.0 (α-polypeptides) and 5.5–8.5 (β-polypeptides). The Dynamic Light Scattering (DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of 5.8 ± 0.1 nm confirming the trimeric nature of the protein. The Circular Dichroism (CD) spectra showed both α-helices and β-sheets in the native conformation of the trimeric protein. The pure cruciferin protein (40 mg/ml) was successfully crystallized; however, the crystals diffracted only to low resolution data (8 Å). Small-angle x-ray scattering (SAXS) was applied to gain insights into the three-dimensional structure in solution. SAXS showed that the radius of gyration is 4.24 ± 0.25 nm and confirmed the nearly globular shape. The SAXS based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins (PDB ID: 3KGL ) of B. napus which further confirmed a highly similar molecular weight and globular shape indicating a conserved trimerization of B. nigra cruciferin. The comparison of the scattering patterns of both proteins showed a minimized χ 2 -value of 1.337 confirming a similar molecular structure. This is the first report describing the purification and characterization of a cruciferin protein from seeds of B. nigra . [ABSTRACT FROM AUTHOR]

The cyclic voltammetry of both bulk manganese sulfate (BMS) and nano manganese sulfate (NMS) were studied using 0.1M KCl supporting electrolyte and glassy carbon working electrode. The redox behavior for both bulk (BMS) and MnSO4 (NMS) sulfate was studied voltammetrically in presence and absence of Doxorubicin (DR) using three electrodes system, silver-silver chloride (Ag/AgCl), platinum and glassy carbon electrodes. Various scan rates were studied for the redox behaviors for bulk and nano MnSO4 (NMS) alone or in presence of Doxorubicin (DR). Stability constants for the interaction of manganese ions with Doxorubicin (DR) were evaluated. The redox mechanism was discussed. [ABSTRACT FROM AUTHOR]

Background: Snake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America particularly in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. The IC-50 value of four synthesized peptides was studied, towards angiotensin converting enzyme, in order to study the structure-function relationship of these peptides. Results: The purification of the peptides was carried out by size exclusion chromatography, followed by reverse phase chromatography. Sequences of all peptides were determined applying MALDI-TOF/TOF mass spectrometry. These hypotensive peptides bear homology to bradykinin potentiating peptides and venom vasodilator peptide. The peptide with m/z 1355.53 (M + H)+1, and the corresponding sequence ZQWAQGRAPHPP, we identified for the first time. A precursor protein containing a fragment of this peptide was reported at genome level, (Uniprot ID P68515), in Bothrops insularis venom gland. These proline rich hypotensive peptides or bradykinin potentiating peptides are usually present in the venom of Crotalinae, and exhibit specificity in binding to the C domain of somatic angiotensin converting enzyme. Four of these hypotensive peptides, were selected and synthesized to obtain the required quantity to study their IC50 values in complex with the angiotensin converting enzyme. The peptide with the sequence ZLWPRPQIPP displayed the lowest IC50 value of 0.64 μM. The IC50 value of the peptide ZQWAQGRAPHPP was 3.63 μM. Conclusion: The canonical snake venom BPPs classically display the IPP motif at the C-terminus. Our data suggest that the replacement of the highly conserved hydrophobic isoleucine by histidine does not affect the inhibitory activity, indicating that isoleucine is not mandatory to inhibit the angiotensin converting enzyme. The evaluation of IC 50 values show that the peptide with basic pI value exhibits a lower IC 50 value. [ABSTRACT FROM AUTHOR]

8-Hydroxyquinolium chloroacetate ( L1) was synthesized and characterized. The results suggest that L1 loses ethyl chloroacetate ion on coordination at low pH (2-5) and consequently it behaves as 8-hydoxyquinoline ( L2). Cu2+, Co2+, Pt4+, Pd2+, Au3+, Ag+ and Nd3+ complexes derived from L2 have been synthesized and characterized using spectral, magnetic and thermal measurements. L2 acts as a neutral bidentate ligand in the case of Cu2+, Co2+, Pt4+, Pd2+ and Nd3+ complexes and as a mononegative bidentate ligand in the case of Au3+ and Ag+ complexes. Octahedral geometry is proposed for Cu2+, Co2+ (grey) and Pt4+ complexes and square-planar for Co2+ (green), Pd2+ and Au3+ complexes. The bond lengths, bond angles, chemical reactivities, binding energies and dipole moments for all compounds were evaluated using density functional theory and molecular electrostatic potential for L1. Superoxide dismutase radical scavenger-like activity and cytotoxic activity of the complexes towards HepG2 liver cancer cells has been screened. Cytotoxicity measurements show that Ag+ and Pd2+ complexes have the highest cytotoxic activity while L1, Cu2+, Co2+ (grey), Co2+ (green), Pt4+ and Nd3+ complexes have no cytotoxic activity. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nanocomposite of ZnO/TiO 2 coated by a mononuclear copper (II) di-Schiff base complex (Cu(LAm) 2) was synthesized. • Characterizations of ZnO/TiO 2 and Cu(LAm) 2 @ZnO/TiO 2) nanocomposites were investigated. • The antimicrobial reactivity were examined for both materials and their supports (HLAm and TiO 2 /ZnO). • DNA interaction was studied by electrophoresis technique. Treatment of 2-((4-hydroxybenzylidene)amino)phenol (HLAm) with Cu(II) ion of 2: 1 stoichiometric ratios, respectively, produced copper (II) di-Schiff base complex (Cu(LAm) 2). HLAm and Cu(LAm) 2 were characterized by using different spectroscopic tools (UV–Vis., IR, and mass spectra), and by CHN percentage analyses (EA). Cu(LAm) 2 was appended on the core/shell of zinc oxide and titanium oxide (TiO 2 /ZnO nanostructured species) within the deprotonated p -hydroxy group of the coordinated ligand. Various analytical tools were demonstrated to distinguish the internal structure and morphological features of the immobilized Cu-complex on TiO 2 /ZnO (Cu(LAm) 2 @TiO 2 /ZnO), as nanocomposite species using XRD, FESEM, HRTEM, IR and EDS spectra, furthermore with thermogravimetric analyses (TGA). TiO 2 was prepared from natural sources (Saussurea costus). For the therapeutic interest, the antimicrobial action of HLAm, Cu(LAm) 2 , TiO 2 /ZnO, Cu(LAm) 2 , and Cu(LAm) 2 @TiO 2 /ZnO against the growth of some common bacteria and fungi were examined. Cu(LAm) 2 and Cu(LAm) 2 @TiO 2 /ZnO displayed the highest action for the inhibition of their growth. The higher action of Cu(LAm) 2 and Cu(LAm) 2 @TiO 2 /ZnO over the free ligand HLAm and TiO 2 /ZnO core/shell was built on the behavior of Cu2+ ion in Schiff base coordination compound (Tweedy's chelation effect). Their reactivity with Genomic DNA was estimated within electrophoresis. As a biomedical candidate, Cu(LAm) 2 and the immobilized Cu(LAm) 2 on TiO 2 /ZnO nanoparticles could undergo further medicinal investigations according to the antimicrobial observations. [ABSTRACT FROM AUTHOR]

Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation. [ABSTRACT FROM AUTHOR]

This study evaluated the biochemical, molecular, and histopathological mechanisms involved in the hypoglycaemic effect of zinc oxide nanoparticles (ZnONPs) in experimental diabetic rats. ZnONPs were prepared by the sol–gel method and characterised by scanning and transmission electron microscopy (SEM and TEM). To explore the possible hypoglycaemic and antioxidant effect of ZnONPs, rats were grouped as follows: control group, ZnONPs treated group, diabetic group, and diabetic + ZnONPs group. Upon treatment with ZnONPs, a significant alteration in the activities of superoxide dismutase, glutathione peroxidase, and the levels of insulin, haemoglobin A1c, and the expression of cluster of differentiation 4+ (CD4+), CD8+ T cells, glucose transporter type‐4 (GLUT‐4), tumour necrosis factor, and interleukin‐6 when compared to diabetic and their control rats. ZnONPs administration to the diabetic group showed eminent blood glucose control and restoration of the biochemical profile. This raises their active role in controlling pancreas functions to improve glycaemic status as well as the inflammatory responses. Histopathological investigations showed the non‐toxic and therapeutic effect of ZnONPs on the pancreas. TEM of pancreatic tissues displayed restoration of islets of Langerhans and increased insulin‐secreting granules. This shows the therapeutic application of ZnONPs as a safe anti‐diabetic agent and to have a potential for the control of diabetes. [ABSTRACT FROM AUTHOR]

Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activity relationship to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. Collectively, we present new organoselenide compounds with cytoprotective and antioxidant properties that can be considered as promising drug candidates for myelin diseases. [ABSTRACT FROM AUTHOR]

A 55 kDa cruciferin protein has been purified and characterized from seeds of Moringa oleifera plant. Protein blast of N-terminal amino-acid sequence showed 60 % sequence similarity with cruciferin from Brassica napus. The M. oleifera protein has been crystallized applying the sitting drop method using 5 % polyethylene glycol 8,000, 38.5 % 3-methyl-1,5-pentanediol and 0.1 M sodium cacodylate pH 6.5. The crystals belonged to the P6322 hexagonal space group with cell dimensions, a = b = 98.4, c = 274.3 Å. Initial diffraction data have been collected to a resolution of 6 Å. [ABSTRACT FROM AUTHOR]