Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q

Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B cells. No significant enhancement of Ig production by B cells was seen in the absence of T cells or PWM. The contribution of T cells or PWM could be replaced by supernatants of PMA and Con A-activated PBMC (T cell growth factor). C1q that had been frozen, in contrast with freshly isolated C1q, was at least 3 times more active in enhancement of the production of Ig by B cells in culture in the presence of suboptimal concentrations of T cell growth factor. The capability of C1q to stimulate B cells could be ascribed to aggregates of C1q. Monomeric C1q was only marginally active to stimulate B cell Ig production, whereas dimeric and tetrameric C1q were able to enhance Ig production by B cells in relation to their size. Furthermore, aggregation of C1q on soluble aggregates of rabbit IgM also increased its potential to enhance B cell Ig production. The interaction of C1q with the B cells occurs via the collagenous tail of C1q, as suggested by inhibition experiments with purified collagenous tails and globular heads of C1q. These results indicate that triggering of C1qR on B cells positively regulates Ig production in vitro.     

D,L-Sulforaphane Loaded Fe3O4@ Gold Core Shell Nanoparticles: A Potential Sulforaphane Delivery System

A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-x_L), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-x_L genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells.     

Isolation, characterization, and mechanism of action of rat beta 1H

beta 1Hrat was purified to homogeneity from fresh rat plasma by precipitation with 28.6% ammonium sulfate followed by sequential chromatography on DEAE-Sephacel, Biorex-70, and gel filtration on Sephacryl-S300. The final material was homogeneous on SDS-PAGE analysis and had an apparent m.w. of 150,000. Reduction with dithiothreitol did not affect its m.w., suggesting that the molecule is composed of one polypeptide chain. The recovery of beta 1H was approximately 10%. A monospecific antibody against beta 1Hrat was obtained from immunized rabbits, which recognized beta 1Hrat as a protein with beta-electrophoretic mobility upon immunoelectrophoresis of fresh rat plasma. The concentration of beta 1H in plasma of normal 4-mo-old Wistar rats was 243.5 +/- 36.3 micrograms/ml (mean +/- S.D.). beta 1Hrat in this study was detected by its capacity to inhibit formation of the P-stabilized cell-bound amplification C3/C5 convertase composed of cell-bound C3bhu and Bbhu. Purified beta 1Hrat produced a dose-related, first-order loss of convertase function and release of 126I-Bbhu from the P-stabilized C3bhuBbhu convertase, indicating a mechanism of action by decay-dissociation of Bbhu from the complex C3bhuBbhuP. beta 1Hrat was at least four times less effective than beta 1Hhu in release of 125I-Bbhu from the homologous convertase composed of C3bhu and Bbhu. On the other hand beta 1H was twice as effective in releasing 125I-Bbrat from the convertase composed of C3bratBbratP when compared to beta 1Hhu. These differences are presumably dependent upon the species-specific affinity of beta 1H from humans or rats for C3bhu or C3brat, respectively.     

Nanomolar detection of hydrogen peroxide at a new polynuclear cluster of tin pentacyanonitrosylferrate nanoparticle-modified carbon ceramic electrode

This work describes a new electrochemical sensor for hydrogen peroxide based on tin pentacyanonitrosylferrate (SnPCNF)-modified carbon ceramic electrode (CCE). The modified electrode was constructed by using a sol-gel technique involving two steps: construction of CCE containing metallic tin (Sn) powder and then electrochemical creation of SnPCNF film on the surface of CCE. The modified electrode was characterized by energy-dispersive X-ray, Fourier transform infrared, scanning electron microscopy, and cyclic voltammetry (CV) techniques. The charge transfer coefficient (α) and charge transfer rate constant (k_s) for the modifying film were calculated. The electrocatalytic activity of the modified electrode toward the reduction of hydrogen peroxide was studied by CV and chronoamperometry. A linear calibration curve was obtained over the hydrogen peroxide concentration range of 0.5 to 69.4 μM using a hydrodynamic amperometric technique. The limit of detection (for a signal-to-noise ratio of 3) and sensitivity were found to be 92 nM and 0.89 μA/μM, respectively. Furthermore, the diffusion coefficient of hydrogen peroxide (D) and catalytic rate constant (k_cat) were calculated.     

The protein kinase YakA regulates g-protein-linked signaling responses during growth and development of Dictyostelium.

A genetic screen for Dictyostelium mutants that phenotypically resemble cells lacking the G-protein beta-subunit yielded the protein kinase YakA. Like gbeta-null cells, yakA-null cells fail to enter development and display slow growth on bacterial lawns. We created a temperature-sensitive yakA mutant and showed that YakA activity is required not only at the onset but also during development. The yakA-null cells have strong defects in folic acid-induced responses, such as actin polymerization and cGMP accumulation, indicating that they play a role in G-protein-mediated signaling responses. We propose that YakA acts downstream of G-proteins, because cAMP receptors still couple to G-proteins in the yakA mutant. In addition, the previously observed growth arrest induced by overexpression of YakA also occurs in gbeta mutants. We localized YakA-GFP to the cytosol suggesting that YakA may be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3, a subclass of dual-specificity Yak-related kinases (Dyrk) with unknown function.     

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability.     

Two new species of Chrysis Linnaeus (Hymenoptera,Chrysididae) from Iran

The Iranian species in the Chrysis pulchella and C. varidens species groups are investigated. Six species are recognized, two of which are described for the first time: Chrysis gamberoonensis Farhad, Rosa and Talebi sp. nov. and Chrysis brunneamarginata Farhad, Rosa and Talebi sp. nov.. Chrysis gamberoonensis Farhad, Rosa and Talebi sp. nov. belongs to the C. pulchella group and is recognizable within this species group by its unique blue body coloration, scattered mesosoma punctures, polished pit row with elongated pits, and a small median tooth on the lateral edge of metasomal tergum 3. Chrysis brunneamarginata Farhad, Rosa and Talebi sp. nov. belongs to the C. varidens group and is recognizable by the usually colorless apical rim of metasomal tergum 3, and the unique shape of the anterior corners of the scutellum which are enlarged, thickened and directed backward covering the axillary trough. Dichotomous keys and distributional data for Iranian species included in these species groups are provided. Chrysis schwarzi Linsenmaier, 1968 is raised to species rank. The number of Iranian Chrysis species and subspecies is raised to 122.www.zoobank.org/urn:lsid:zoobank.org:pub:F419F860-3B90-4679-9A19-2CF5C255AE6B