Sphingosine-1-Phosphate-Triggered Expression of Cathelicidin LL-37 Promotes the Growth of Human Bladder Cancer Cells

It has been proven that tumour growth and progression are regulated by a variety of mediators released during the inflammatory process preceding the tumour appearance, but the role of inflammation in the development of bladder cancer is ambiguous. This study was designed around the hypothesis that sphingosine-1-phosphate (S1P), as a regulator of several cellular processes important in both inflammation and cancer development, may exert some of the pro-tumorigenic effects indirectly due to its ability to regulate the expression of human cathelicidin (hCAP-18). LL-37 peptide released from hCAP-18 is involved in the development of various types of cancer in humans, especially those associated with infections. Using immunohistological staining, we showed high expression of hCAP-18/LL-37 and sphingosine kinase 1 (the enzyme that forms S1P from sphingosine) in human bladder cancer cells. In a cell culture model, S1P was able to stimulate the expression and release of hCAP-18/LL-37 from human bladder cells, and the addition of LL-37 peptide dose-dependently increased their proliferation. Additionally, the effect of S1P on LL-37 release was inhibited in the presence of FTY720P, a synthetic immunosuppressant that blocks S1P receptors. Together, this study presents the possibility of paracrine relation in which LL-37 production following cell stimulation by S1P promotes the development and growth of bladder cancer.     

Ladder-like Polymer Brushes Containing Conjugated Poly(Propylenedioxythiophene) Chains

The high stability and conductivity of 3,4-disubstituted polythiophenes such as poly(3,4-ethylenedioxythiophene) (PEDOT) make them attractive candidates for commercial applications. However, next-generation nanoelectronic devices require novel macromolecular strategies for the precise synthesis of advanced polymer structures as well as their arrangement. In this report, we present a synthetic route to make ladder-like polymer brushes with poly(3,4-propylenedioxythiophene) (PProDOT)-conjugated chains. The brushes were prepared via a self-templating surface-initiated technique (ST-SIP) that combines the surface-initiated atom transfer radical polymerization (SI-ATRP) of bifunctional ProDOT-based monomers and subsequent oxidative polymerization of the pendant ProDOT groups in the parent brushes. The brushes prepared in this way were characterized by grazing-angle FTIR, XPS spectroscopy, and AFM. Steady-state and time-resolved photoluminescence measurements were used to extract the information about the structure and effective conjugation length of PProDOT-based chains. Stability tests performed in ambient conditions and under exposure to standardized solar light revealed the remarkable stability of the obtained materials.     

Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease. In many cases, HCC is an effect of chronic liver inflammation, which leads to the formation of a complex tumor microenvironment (TME) composed of immune and stromal cells. The TME of HCC patients is a challenge for therapies, as it is involved in metastasis and the development of resistance. However, given that the TME is an intricate system of immune and stromal cells interacting with cancer cells, new immune-based therapies are being developed to target the TME of HCC. Therefore, understanding the complexity of the TME in HCC will provide new possibilities to design novel and more effective immunotherapeutics and combinatorial therapies to overcome resistance to treatment. In this review, we describe the role of inflammation during the development and progression of HCC by focusing on TME. We also describe the most recent therapeutic advances for HCC and possible combinatorial treatment options.     

Discrimination between NSIP- and IPF-Derived Fibroblasts Based on Multi-Parameter Characterization of Their Growth,Morphology and Physic-Chemical Properties

Background: The aim of the research presented here was to find a set of parameters enabling discrimination between three types of fibroblasts, i.e., healthy ones and those derived from two disorders mimicking each other: idiopathic pulmonary fibrosis (IPF), and nonspecific interstitial pneumonia (NSIP). Methods: The morphology and growth of cells were traced using fluorescence microscopy and analyzed quantitatively using cell proliferation and substrate cytotoxicity indices. The viability of cells was recorded using MTS assays, and their stiffness was examined using atomic force microscopy (AFM) working in force spectroscopy (FS) mode. To enhance any possible difference in the examined parameters, experiments were performed with cells cultured on substrates of different elasticities. Moreover, the chemical composition of cells was determined using time-of-flight secondary ion mass spectrometry (ToF-SIMS), combined with sophisticated analytical tools, i.e., Multivariate Curve Resolution (MCR) and Principal Component Analysis (PCA). Results: The obtained results demonstrate that discrimination between cell lines derived from healthy and diseased patients is possible based on the analysis of the growth of cells, as well as their physical and chemical properties. In turn, the comparative analysis of the cellular response to altered stiffness of the substrates enables the identification of each cell line, including distinguishing between IPF- and NSIP-derived fibroblasts.     

The Multifaceted Roles of Mast Cells in Immune Homeostasis,Infections and Cancers

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens. MCs can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, MCs indeed mediate acute inflammatory responses such as those evident in allergic reactions. Furthermore, MCs participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. The control of MC activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, MCs contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells. In this review, we provide a comprehensive overview of the functions of MCs in health and disease. Further, we discuss how mouse models of MC deficiency have become useful tools for establishing MCs as a potential cellular target for treating inflammatory disorders.     

Influence of the fly ash fraction after grinding process on the hydrothermal synthesis efficiency of Na-A,Na-P1,Na-X and sodalite zeolite types

The fly ashes(Class F and C)have been successfully used as the main substrates in the hydrothermal syntheses of Na-A,Na-P1,Na-X and sodalite zeolites.Both ashes...     

Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors

Corticotroph pituitary adenomas commonly cause Cushing’s disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3′ UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.