Highly Stable Antitumor Silver-Lipid Nanoparticles Optimized for Targeted Therapy.

Background: Silver nanoparticles (AgNPs) have a broad spectrum of biocidal effects, allowing also their antitumor application. To enhance bioavailability, minimize adverse effects and enable targeted drug delivery AgNPs may be encapsulated in liposomes. In this study we aimed to create highly stable and effective antitumor AgNP lipid formulations (LAgs).

Cardiac effects of OPA1 protein promotion in a transgenic animal model.

Mitochondria form a dynamic network in cells, regulated by the balance between mitochondrial fusion and fission. The inhibition of mitochondrial fission can have positive effects in acute ischemic/reperfusion injury models by preventing the fall in mitochondrial membrane potential associated with fission processes. However, inhibition of fission in chronic models is disadvantageous because it obstructs the elimination of damaged mitochondrial fragments.

Exploring the Chemical Profile, In Vitro Antioxidant and Anti-Inflammatory Activities of Extracts.

In this study, the phytochemical composition, in vitro antioxidant, and anti-inflammatory effects of the aqueous and 60% ethanolic (EtOH) extracts of leaf, flower, and root were examined. The antioxidant activity of extracts was determined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. The total phenolic content (TPC) of the extracts was measured by the Folin-Ciocalteu assay.

Emerging Lipid Targets in Glioblastoma.

GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM.

Decreased Expression of in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival.

Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein subfamily, is predominantly expressed in the brain and placenta in humans. Recently, we unveiled that ZNF554 regulates trophoblast invasion during placentation and its decreased expression leads to the early pathogenesis of preeclampsia. Since ZNF proteins are immensely implicated in the development of several tumors including malignant tumors of the brain, here we explored the pathological role of ZNF554 in gliomas.

Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To improve pre- and post-operative diagnosis and prognosis novel molecular markers are desirable. Here we used MALDI imaging mass spectrometry (IMS) and immunohistochemistry (IHC) to seek tumor specific expression of proteins and lipids in HNSCC samples.

Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia.

The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells.

Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response.

Galectins are potent immunomodulators that regulate maternal immune responses in pregnancy and prevent the rejection of the semi-allogeneic fetus that also occurs in miscarriages. We previously identified a gene cluster on Chromosome 19 that expresses a subfamily of galectins, including galectin-13 (Gal-13) and galectin-14 (Gal-14), which emerged in anthropoid primates. These galectins are expressed only by the placenta and induce the apoptosis of activated T lymphocytes, possibly contributing to a shifted maternal immune balance in pregnancy.

Proteomic identification of membrane-associated placental protein 4 (MP4) as perlecan and characterization of its placental expression in normal and pathologic pregnancies.

Background: More than 50 human placental proteins were isolated and physico-chemically characterized in the 70-80s by Hans Bohn and co-workers. Many of these proteins turned to have important role in placental functions and diagnostic significance in pregnancy complications. Among these proteins was membrane-associated placental protein 4 (MP4), for which identity or function has not been identified yet.

Increased placental expression of Placental Protein 5 (PP5) / Tissue Factor Pathway Inhibitor-2 (TFPI-2) in women with preeclampsia and HELLP syndrome: Relevance to impaired trophoblast invasion?

Introduction: Placental Protein 5 (PP5)/Tissue Factor Pathway Inhibitor-2 (TFPI-2) is an extracellular matrix-associated protein mainly expressed by the syncytiotrophoblast that may regulate trophoblast invasion. Our aim was to study placental PP5/TFPI-2 expression and its relation to placental pathology in various forms of preeclampsia and HELLP syndrome.

Methods: Placental and maternal blood specimens were collected at the time of delivery from the same women in the following groups: 1) early controls; 2) early preeclampsia; 3) early preeclampsia with HELLP syndrome; 4) late controls; and 5) late preeclampsia.

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor.

The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored.

Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia.

Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes.

Cell surface localised Hsp70 is a cancer specific regulator of clathrin-independent endocytosis.

The stress inducible heat shock protein 70 (Hsp70) is present specifically on the tumour cell surface yet without a pro-tumour function revealed. We show here that cell surface localised Hsp70 (sHsp70) supports clathrin-independent endocytosis (CIE) in melanoma models. Remarkably, ability of Hsp70 to cluster on lipid rafts in vitro correlated with larger nano-domain sizes of sHsp70 in high sHsp70 expressing cell membranes.

Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells.

The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated in the modulation of T cell responses, but the underlying molecular mechanism of CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T cells stimulated via anti-CD3ε- or anti-CD59-coated surfaces, using time-resolved single-cell Ca(2+) imaging as a read-out for stimulation. This analysis revealed a heterogeneous Ca(2+) response of the cell population in a stimulus-dependent manner.

The complex function of hsp70 in metastatic cancer.

Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a "chaperokine", activating antitumor immunity.

High-throughput, multiparameter analysis of single cells.

Heterogeneity of cell populations in various biological systems has been widely recognized, and the highly heterogeneous nature of cancer cells has been emerging with clinical relevance. Single-cell analysis using a combination of high-throughput and multiparameter approaches is capable of reflecting cell-to-cell variability, and at the same time of unraveling the complexity and interdependence of cellular processes in the individual cells of a heterogeneous population. In this review, analytical methods and microfluidic tools commonly used for high-throughput, multiparameter single-cell analysis of DNA, RNA, and proteins are discussed.

Casein kinase 2-interacting protein-1, an inflammatory signaling molecule interferes with TNF reverse signaling in human model cells.

When transmembrane form of tumor necrosis factor (mTNF) interacts with its cognate receptors or agonistic antibodies signaling pathways are activated in the ligand expressing cells. This "reverse signaling" appears a fine-tuning control mechanism in the immune response. Despite a clinical relevance key molecules of TNF reverse signaling and their functions remain elusive.

Importance of reverse signaling of the TNF superfamily in immune regulation.

TNF-related ligands (with the exception of lymphotoxin-α) are synthesized as type II transmembrane proteins, though many of them also have soluble forms. An increasing number of publications report that these 'ligands' behave as receptors, activating intracellular signaling pathways when interacting with cognate 'receptors' or agonistic antibodies. Most members of the TNF family and their receptors influence survival, proliferation, differentiation or activation of immune cells.

Lysosomal rerouting of Hsp70 trafficking as a potential immune activating tool for targeting melanoma.

Tumor specific cell surface localization and release of the stress inducible heat shock protein 70 (Hsp70) stimulate the immune system against cancer cells. A key immune stimulatory function of tumor-derived Hsp70 has been exemplified with the murine melanoma cell model, B16 overexpressing exogenous Hsp70. Despite the therapeutic potential mechanism of Hsp70 transport to the surface and release remained poorly understood.

A PDMS-based biochip with integrated sub-micrometre position control for TIRF microscopy of the apical cell membrane.

A poly(dimethylsiloxane) (PDMS)-based biochip with an integrated pressure controlled positioning system with sub-micrometre precision was realized. The biochip was easy and cheap to manufacture and enabled positioning in a wet environment. It allowed the application of total internal reflection fluorescence (TIRF) microscopy at the dorsal cell membrane, which is not adhering to a support.

Antitumour properties of acridone alkaloids on a murine lymphoma cell line.

The aim of the present study was to investigate the anticancer properties of a set of furanoacridone alkaloids, arborinine and evoxanthine, including the inhibitory effect of P-glycoprotein (Pgp) and the apoptosis-inducing capacity. The tested alkaloids were evaluated for multidrug resistance (MDR)-reversing activity on human Pgp-transfected L5178 mouse lymphoma cells, using the rhodamine-123 (Rh-123) assay. The antiproliferative effects of natural compounds and their interactions with doxorubicin were determined in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays.

A mutant small heat shock protein with increased thylakoid association provides an elevated resistance against UV-B damage in synechocystis 6803.

Besides acting as molecular chaperones, the amphitropic small heat shock proteins (sHsps) are suggested to play an additional role in membrane quality control. We investigated sHsp membrane function in the model cyanobacterium Synechocystis sp. PPC 6803 using mutants of the single sHsp from this organism, Hsp17.

Real-time polymerase chain reaction-based exponential sample amplification for microarray gene expression profiling.

Conventional approaches to target labeling for gene expression analysis using microarray technology typically require relatively large amounts of RNA, a serious limitation when the available sample is limited. Here we describe an alternative exponential sample amplification method by using quantitative real-time polymerase chain reaction (QRT-PCR) to follow the amplification and eliminate the overamplified cDNA which could distort the quantitative ratio of the starting mRNA population. Probes generated from nonamplified, PCR-amplified, and real-time-PCR-amplified cDNA samples were generated from lipopolysaccharide-treated and nontreated mouse macrophages and hybridized to mouse cDNA microarrays.