Polymeric nanoparticles with encapsulated superparamagnetic iron oxide and conjugated Cisplatin for potential bladder cancer therapy

Amphiphilic poly(ε-caprolactone)-b-poly(propargyl methacrylate-click-mercaptosuccinic acid-co-poly(ethylene glycol) methyl ether methacrylate) (PCL-b-P(PMA-click-MSA-co-PEGMA)) were synthesized by a combination of ring-opening polymerization, reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiol-yne "click" reaction. The hydrophobic PCL core can be used to load superparamagnetic iron oxide nanoparticles (SPIONs), while the pendant dicarboxylic groups in the hydrophilic shell are used to coordinate cisplatin. These SPIONs-loaded, cisplatin-conjugated polymeric nanoparticles (Pt-Fe-PNs) are superparamagnetic at room temperature and are mucoadhesive. Release of cisplatin from Pt-Fe-PNs in artificial urine at 37 °C was characterized by an initial burst release with a release of ～30% of the cisplatin in the first 4 h followed by a slow sustained release over 4 days. The cisplatin release can be further enhanced by increasing the temperature. These Pt-Fe-PNs can effectively induce cytotoxicity against UMUC3 bladder cancer cells with IC(50) of 32.3 μM. These results indicate that Pt-Fe-PNs is potentially a promising cisplatin delivery vehicle which can be combined with SPIONs-induced hyperthermia for bladder cancer therapy.     

Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes

Mesenchymal stem cells(MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T(Treg) and B(Breg) cells. The induction of Treg and Breg cells is of particular interest since Treg and Breg cells have significant roles in maintaining immune tolerance. Several mechanisms have been proposed regarding to the MSCs-mediated induction of Treg and Breg cells. Accordingly, MSCs induce regulatory lymphocytes through secretion of multiple pleiotropic cytokines, cell-to-cell contact with target cells and modulation of antigen-presenting cells. Here, we summarized how MSCs induce Treg and Breg cells to provoke immunosuppression.     

Circulating myeloid dendritic cells of advanced cancer patients result in reduced activation and a biased cytokine profile in invariant NKT cells

CD1d-restricted invariant NKT (iNKT) cells play important regulatory roles in various immune responses, including antitumor immune responses. Previous studies have demonstrated quantitative and qualitative defects in iNKT cells of cancer patients, and these defects are clinically relevant as they are associated with poor prognosis. In this study we demonstrate that defects in the iNKT cell population can, at least in part, be attributed to defective interactions between iNKT cells and CD1d-expressing circulating myeloid dendritic cells (mDC), as mDC of patients with advanced melanoma and renal cell cancer reduced the activation and Th1 cytokine production of healthy donor-derived iNKT cells. Interestingly, this reduced activation of iNKT cells was restricted to patients with low circulating iNKT cell numbers and could be reversed by IL-12 and in part by the neutralization of TGF-beta, but it was further reduced by the neutralization of IL-10 in vitro. Additional experiments revealed discordant roles for TGF-beta and IL-10 on human iNKT cells, because TGF-beta suppressed iNKT cell activation and proliferation and IFN-gamma production while IL-10 was identified as a cytokine involved in stimulating the activation and expansion of iNKT cells that could subsequently suppress NK cell and T cell responses.     

Molecular phylogeny of diplomonads and enteromonads based on SSU rRNA,alpha-tubulin and HSP90 genes: Implications for the evolutionary history of the double karyomastigont of diplomonads

Background  

Fornicata is a relatively recently established group of protists that includes the diplokaryotic diplomonads (which have two similar nuclei per cell), and the monokaryotic enteromonads, retortamonads and Carpediemonas, with the more typical one nucleus per cell. The monophyly of the group was confirmed by molecular phylogenetic studies, but neither the internal phylogeny nor its position on the eukaryotic tree has been clearly resolved.     

Statins but not fibrates improve the atherogenic to anti-atherogenic lipoprotein particle ratio: a randomized crossover study

Background  

Prior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis. Knowledge of effects of lipid lowering drugs on lipoprotein subclasses is useful. We treated subjects with hyperlipidemia sequentially with statins and fibrates, the 2 main classes of lipid lowering therapy and studied changes in NMR lipoprotein subclasses.     

Expression of truncated phosphoproteins of Nipah virus and Hendra virus in <Emphasis Type="Italic">Escherichia coli</Emphasis> for the differentiation of henipavirus infections

The genus Henipavirus in the family Paramyxoviridae compromises two newly identified dangerous pathogens, Nipah virus and Hendra virus. Phosphoprotein of the two viruses is one of the major immunodominant antigens and the most divergent protein in the viral genomes. We have now expressed two pairs of truncated phosphoproteins of the two viruses in Escherichia coli in a soluble form using a vector tailored from pET32a. The truncated recombinant phosphoproteins were purified with His-Tag affinity chromatography and their antigenicity was determined by western blotting and ELISA. The longer pair of truncated recombinant phosphoproteins, covering amino acid residues 4–550, was more antigenic than the shorter one and of potential utility in the serological differentiation of henipavirus infections.     

New insights in Salicornia L. and allied genera (Chenopodiaceae) inferred from nrDNA sequence data

A phylogenetic analysis was performed based on ITS DNA sequences of fourteen samples from different sources of six species of Salicornia, the three allied genera Arthrocnemum, Sarcocornia and Halocnemum of the same tribe Salicornieae, and other genera of the subfamily Salicornioideae used in previous studies. Bassia hirsuta, Camphorosma monspeliaca (subfamily Chenopodioideae) and four species of Suaeda (subf. Suaedoideae) were chosen as outgroups. Results show that the annual genus Salicornia is a sister group to the perennial genera Sarcocornia, Arthrocnemum and Halocnemum. Moreover, the phylogenetic analysis based on ITS results distinguished two groups of Salicornia species which fitted with ploidy level: one group consisted of diploid species, and the second of tetraploid ones. Sarcocornia and Arthrocnemum are shown to be closely related, even though the species investigated here exhibited an evident distance between their ITS sequences. On the basis of our results, these two genera should be united. Bienertia (already separated as Bienertieae) was confirmed as probable outgroup to the subf. Salicornioideae, while Kalidium (subf. Salicornioideae, tribe Halopeplideae) was an outgroup to the rest of the Salicornioideae (tribe Salicornieae). The group Allenrolfea plus Halocnemum was the most basal of the tribe Salicornieae amongst those investigated in this study. The two samples of Halocnemum strobilaceum used in this work displayed numerous changes (transitions and transversions) in their respective sequences, probably related to their morphological and chorological differentiation. On the basis of our analysis, the most probable basal chromosome number for Salicornieae appears to be 2n = 18. The same number would also be the base number for the annual genus Salicornia and the perennial Arthrocnemum ( + Sarcocornia), with polyploidy arising independently in the two groups.     

Fatty acid production by heterotrophic Chlorella saccharophila

The fatty acid composition of the alga Chlorella saccharophila was investigated under different growth conditions. Using glucose as the sole carbon source, heterotrophically-grown Chlorella saccharophila produced a greater proportion of the polyunsaturated fatty acids (C18: 2 and C18: 3) than photosynthetic cultures, with linoleic acid (C18: 2) predominating. An unexpected discovery was the observation that at the lowest glucose concentration (2.5 gl^–1) the lipid content of the algae increased to between 36–47% of the cell weight, depending on the temperature. At glucose concentrations of 5 g l^–1 or more, the lipid content fell to 10–12% of the cell, although total fatty acid yield was higher due to higher biomass concentrations. Aeration of heterotrophic cultures promoted the production of unsaturated fatty acids compared to non-aerated cultures.