Plasma levels of BAFF and APRIL are elevated in patients with asthma in Saudi Arabia.

B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor superfamily of cytokines and can induce B cell activation, differentiation, and antibody production via interaction with their receptors, including transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and B-cell activating factor receptor (BAFF-R). Herein, we assessed the plasma protein levels of BAFF and APRIL in patients with asthma to determine whether their expression is correlated with total IgE production and examined the surface expression of BAFF/APRIL receptors on B cells. Blood samples were collected from 47 patients with controlled asthma symptoms and 20 healthy normal controls, and plasma levels of APRIL, BAFF, and total IgE protein were quantified by corresponding ELISA assays. Furthermore, lymphocytes were isolated and B cells were analyzed for the presence of BAFF-R, BCMA, and TACI receptors using flow cytometry. Our results showed that IgE, BAFF, and APRIL plasma levels were markedly increased in patients with asthma compared with healthy controls. Moreover, expression of BAFF-R and BCMA, but not that of TACI, was significantly increased in patients with asthma compared with healthy controls. Overall, the findings suggest BAFF and APRIL as key mediators of asthma, and determination of their plasma levels may be useful in monitoring asthma symptoms and treatment response.

Proteomics-based identification of cancer-associated proteins in chronic lymphocytic leukaemia

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. RESULTS: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p 0.05). CONCLUSIONS: Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease.

Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells.

INTRODUCTION: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. OBJECTIVE: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. METHODS: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. RESULTS: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p≤0.008 with corrected p≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in "response to zinc", "response to toxic substance" and "negative regulation of growth" (corrected p≤0.05). In contrast, the repressed genes positively regulated "cell proliferation", "cell migration", "cell adhesion", "receptor signaling pathway via JAK-STAT" and "phosphatidylinositol 3-kinase signaling" (corrected p≤0.05). Lowering the FC to ≥1.5 with p≤0.05 and corrected p≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. CONCLUSION: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.

In vitro biological evaluation of anti-diabetic activity of organic-inorganic hybrid gold nanoparticles.

Diabetes mellitus has been considered as a heterogeneous metabolic disorder characterised by complete or relative impairment in the production of insulin by pancreatic ß-cells or insulin resistance. In the present study, propanoic acid, an active biocomponent isolated from Cassia auriculata is employed for the synthesis of propanoic acid functionalised gold nanoparticles (Pa@AuNPs) and its anti-diabetic activity has been demonstrated in vitro. In vitro cytotoxicity of synthesised Pa@AuNPs was performed in L6 myotubes. The mode of action of Pa@AuNPs exhibiting anti-diabetic potential was validated by glucose uptake assay in the presence of Genistein (insulin receptor tyrosine kinase inhibitor) and Wortmannin (Phosphatidyl inositide kinase inhibitor). Pa@AuNPs exhibited significant glucose uptake in L6 myotubes with maximum uptake at 50 ng/ml. Assays were performed to study the potential of Pa@AuNPs in the inhibition of protein-tyrosine phosphatase 1B, α-glucosidases, and α-amylase activity.

Distribution of biocide resistant genes and biocides susceptibility in multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii - A first report from the Kingdom of Saudi Arabia.

PURPOSES: The aim of this study was to determine the frequency of biocide resistant genes, qacA, qacE and cepA in multidrug resistant (MDR) bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii and to correlate the presence or absence of resistant genes with biocides susceptibility. MATERIALS AND METHODS: The study included 44 MDR K. pneumoniae, P. aeruginosa and A. baumannii microorganisms. The bacteria were screened for the presence of biocide resistant genes by the polymerase chain reaction (PCR) method. The test organisms were isolated from various clinical specimens in the Qassim region, Saudi Arabia. The in vitro susceptibility tests of the three biocides (benzalkonium chloride, cetrimide and chlorhexidine gluconate) were studied against the test isolates by broth microdilution method following Clinical and Laboratory Standards Institute guidelines. RESULTS: With the distribution of biocide resistant genes in K. pneumoniae, all 9 isolates (100%) possessed cepA; 4 (44.4%) and 1 (11.1%) isolate contained qacA and qacE genes respectively. Among 24 isolates of A. baumannii tested, cepA, qacA and qacE genes were found in 54.2%, 16.7% and 33.3% of isolates respectively. Among 11 P. aeruginosa isolates, 63.6% contained cepA gene, 18.2% contained qacE genes, and none of the isolates harboured qacA gene. There was no significant correlation between presence or absence of biocide resistant genes and high MIC values of the test isolates (p≥0.2). CONCLUSION: Our observations imply that there was no significant correlation between presence or absence of biocide resistant genes and MICs observed in MDR K. pneumoniae, P. aeruginosa and A. baumannii. Further studies are required to find to confirm the trend of reduced susceptibility to biocides of problematic nosocomial pathogens.

Green synthesis of silver nanoparticles for selective toxicity towards cancer cells.

Therapeutic applications of nanoparticles (NPs) are rapidly increasing for their utility in medicine, especially cancer therapy. The present study investigated the green synthesis of silver NPs (Ag NPs) of 10 nm size using Sargassum vulgare and its preferential ability to kill cancerous human myeloblastic leukemic cells HL60 and cervical cancer cells HeLa as compared with normal peripheral blood mononuclear cells. DNA fragmentation study and annexin V marker fluorescence-activated cell sorting (FACS) analysis revealed the Ag NP-induced cell death is through apoptosis. Transmission electron micrographs have showed the endocytosis of Ag NPs into the nucleus. Ag NPs inhibited the lipid peroxidation-induced reactive oxygen species generation, thus preventing the irradiation-related carcinogenesis. This study suggested that a mechanism underlying the toxicity of Ag NPs towards cancer cells is due to DNA damage and apoptosis. The authors' findings revealed the potential utility of as-prepared Ag NPs in the treatment of cancer as prophylactic agent with antioxidant property and chemotherapeutic agent for their selective toxicity to cancer cells.

Nanostructured molybdenum oxide-based antibacterial paint: effective growth inhibition of various pathogenic bacteria.

The prevention of bacterial infections in the health care environment is paramount to providing better treatment. Covering a susceptible environment with an antimicrobial coating is a successful way to avoid bacterial growth. Research on the preparation of durable antimicrobial coatings is promising for both fundamental surface care and clinical care applications. Herein, we report a facile, efficient, and scalable preparation of MoO3 paint using a cost-effective ball-milling approach. The MoO3 nanoplates (synthesized by thermal decomposition of ammonium heptamolybdate) are used as a pigment and antibacterial activity moiety in alkyd resin binders and other suitable eco-friendly additives in the preparation of paint. Surface morphology, chemical states, bonding nature, and intermolecular interaction between the MoO3 and the alkyd resin were studied using Raman and x-ray photoelectron spectroscopic analysis. The antibacterial properties of a prepared MoO3 nanoplate against various bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae) was determined using the microdilution method. Bacterial strains exposed to an MoO3 paint coated surface exhibit a significant loss of viability in a time-dependent manner. Fundamental modes of antibacterial activities ascribed from a biocompatible and durable MoO3 nanostructure incorporated into an alkyd resin complex are discussed. The obtained experimental findings suggest the potential utility of prepared MoO3-based paint coating for the prevention of health care associated infections.

Antioxidant & anticancer activities of isatin (1H-indole-2,3-dione), isolated from the flowers of Couroupita guianensis Aubl.

BACKGROUND & OBJECTIVES: Derivatives of isatin are known to have cytotoxicity against human carcinoma cell lines. This compound therefore, has a potential to be used as a chemotherapeutic agent against cancer. This study was done to investigate the antioxidant and anticancer activities of isatin, extracted from flower of a folklore medicinal plant Couroupita guianensis against human promylocytic leukemia (HL60) cells. METHODS: Active fractions demonstrating anticancer and antioxidant activities were isolated from the extracts of shade-dried flowers of C. guianensis by bioassay guided fractionation. The free radical scavenging activity was determined using lipid peroxidation assay. Cytotoxicity against human promylocytic leukemia HL60 cells was determined by MTT assay. Apoptotic activity was analyzed by DNA fragmentation and flowcytometry. RESULTS: Isatin isolated from the active fraction showed antioxidant activity with the EC(50) value of 72.80 µg/ml. It also exhibited cytotoxicity against human promylocytic leukemia HL60 cells in dose-dependant manner with the CC(50) value of 2.94 µg/ml. The isatin-treated cells underwent apoptosis and DNA fragmentation. Apoptosis was confirmed by the FACS analysis using FITC-annexin V markers. INTERPRETATION & CONCLUSIONS: Isatin showed antioxidant activity and was cytotoxic to the HL60 cells due to induction of apoptosis. The isatin can be further evaluated to be used as a prophylactic agent to prevent the free radical-induced cancer and as a chemotherapeutic agent to kill the cancer cells.

Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation.

Nanoparticles are increasingly recognized for their utility in biological applications including nanomedicine. The present study investigated the toxicity of zinc oxide (ZnO) nanoparticles toward prokaryotic and eukaryotic cells. Cytotoxicity of ZnO to mammalian cells was studied using human myeloblastic leukemia cells (HL60) and normal peripheral blood mononuclear cells (PBMCs). Antibacterial activity of ZnO was also tested against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, as well as the Gram-positive bacterium Staphylococcus aureus, and the effect was more pronounced with the Gram-positive than the Gram-negative bacteria. ZnO nanoparticles exhibited a preferential ability to kill cancerous HL60 cells as compared with normal PBMCs. The nanoparticles enhanced ultrasound-induced lipid peroxidation in the liposomal membrane. The work suggested two mechanisms underlying the toxicity of ZnO: (i) involvement of the generation of reactive oxygen species (ROS) and (ii) induction of apoptosis. The work also revealed potential utility of ZnO nanoparticles in the treatment of cancer, for their selective toxicity to cancer cells. FROM THE CLINICAL EDITOR: The toxicity of zinc oxide to bacteria was related to the generation of reactive oxygen species and to the induction of apoptosis. Interestingly, these effects were differentially greater in human myeloblastic leukemia cells (HL60) than normal peripheral blood mononuclear cells.

Synthesis, anticancer and antioxidant activities of 7-methoxyisoflavanone and 2,3-diarylchromanones.

A convenient, fast and high yielding method for the preparation of 7-methoxyisoflavanone and 2,3-diarylchromanones has been developed by the condensation of benzyl-2-hydroxy-4-alkoxyphenylketone with arylaldehyde/paraformaldehyde in presence of diethylamine, assisted by microwave activation. All the synthesized compounds were screened for anticancer as well as antioxidant activities. Among the nine compounds, 7-methoxyisoflavanone 7 and diarylchromanone 6c shows potential anticancer activity and diarylchromanone 6b has potential antioxidant activity. Compound 6h possesses anticancer and antioxidant activity at the same concentration.