Biomimetic hierarchical nanofibrous surfaces inspired by superhydrophobic lotus leaf structure for preventing tissue adhesions

Undesirable tissue adhesions remain one of the most common and dreaded postoperative complications. Biocompatible nanofibrous mats with antiadhesive surfaces represent a promising barrier method for preventing the formation of adhesions. The material developed in this work was inspired by the natural superhydrophobic lotus leaf nanostructure, which was mimicked by a unique combination of needleless electrospraying and electrospinning technology of poly-ε-caprolactone (PCL). The surface hydrophobicity of electrosprayed nanodroplets was further enhanced by cold plasma modification using the chemical vapor deposition (CVD) method with hexamethyldisiloxane (HMDSO). The treatment led to a successful decrease in surface wettability of our samples. Morphology (scanning electron microscopy), wettability (contact angle) and chemical composition (FTIR analysis) were observed for a period of six months to track possible changes; the obtained results verified the presence of HMDSO during the whole time period. Cytocompatibility was confirmed in vitro with 3T3 mouse fibroblasts according to the norm ISO 10993-5. Cell adhesion and proliferation were assessed in vitro by metabolic MTT assay and fluorescence microscopy after 4, 7, and 14 days. Antiadhesive behaviour was confirmed by atomic force microscopy and ex vivo by peel test 90° with intestinal tissue, the final structure has a great potential to reduce postoperative tissue adhesions

Diversity, Phylogeny and Expression Patterns of Pou and Six Homeodomain Transcription Factors in Hydrozoan Jellyfish Craspedacusta sowerbyi

Formation of all metazoan bodies is controlled by a group of selector genes including homeobox genes, highly conserved across the entire animal kingdom. The homeobox genes from Pou and Six classes are key members of the regulation cascades determining development of sensory organs, nervous system, gonads and muscles. Besides using common bilaterian models, more attention has recently been targeted at the identification and characterization of these genes within the basal metazoan phyla. Cnidaria as a diploblastic sister group to bilateria with simple and yet specialized organs are suitable models for studies on the sensory organ origin and the associated role of homeobox genes. In this work, Pou and Six homeobox genes, together with a broad range of other sensory-specific transcription factors, were identified in the transcriptome of hydrozoan jellyfish Craspedacusta sowerbyi. Phylogenetic analyses of Pou and Six proteins revealed cnidarian-specific sequence motifs and contributed to the classification of individual factors. The majority of the Craspedacusta sowerbyi Pou and Six homeobox genes are predominantly expressed in statocysts, manubrium and nerve ring, the tissues with sensory and nervous activities. The described diversity and expression patterns of Pou and Six factors in hydrozoan jellyfish highlight their evolutionarily conserved functions. This study extends the knowledge of the cnidarian genome complexity and shows that the transcriptome of hydrozoan jellyfish is generally rich in homeodomain transcription factors employed in the regulation of sensory and nervous functions

Daratumumab for the Treatment of Multiple Myeloma

This mini-review will summarize the present state of development of the CD38 antibody daratumumab for the treatment of multiple myeloma

Harnessing the Immune System to Fight Multiple Myeloma

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects

<i>Craspedacusta sowerbyi</i> body plan scheme.

<p>Radial symmetric body plan of <i>Craspedacusta sowerbyi</i> is divided in subumbrella and exumbrella regions from the side projection. The most distinct features are four gonads and the presence of up to two hundreds of tentacles. Particular organs are described in the scheme. Body size is up to 2.5 cm in diameter.</p

Comparison of phylogenetic trees of HD (A) and SD (B) regions of Six class transcription factors.

<p>The phylogenetic trees were calculated by the maximum likelihood method (WAG protein substitution model, bootstrap 1000) and processed by NJ Plot software. Phylogenetically representative sequences from the following metazoan animals were selected for comparison: sponges (<i>Chalinula loosanoffi, Ephydatia fluviatilis, Sycon calcaravis</i>), cnidarians (<i>Nematostella vectensis</i>, <i>Anthopleura japonica</i>, <i>Podocoryne carnea</i>, <i>Hydra magnipapillata</i>, <i>Cladonema radiatum</i>, <i>Aurelia aurita</i>), invertebrates (<i>Saccoglossus kowalevskii</i>, <i>Drosophila melanogaster</i>, <i>Branchistoma floridae</i>) and vertebrates (<i>Danio rerio</i> and <i>Homo sapiens</i>). For the list of ID numbers of reference sequences see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036420#pone.0036420.s011" target="_blank">Text S1</a>.</p

Daratumumab depletes CD38⁺ immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma

Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with crosslinking. These mechanisms may also target nonplasma cells that express CD38, which prompted evaluation of daratumumab’s effects on CD38-positive immune subpopulations. Peripheral blood (PB) and bone marrow (BM) from patients with relapsed/refractory myeloma from 2 daratumumab monotherapy studies were analyzed before and during therapy and at relapse. Regulatory B cells and myeloid-derived suppressor cells, previously shown to express CD38, were evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting. A novel subpopulation of regulatory T cells (Tregs) expressing CD38 was identified. These Tregs were more immunosuppressive in vitro than CD38-negative Tregs and were reduced in daratumumab-treated patients. In parallel, daratumumab induced robust increases in helper and cytotoxic T-cell absolute counts. In PB and BM, daratumumab induced significant increases in CD8(+):CD4(+) and CD8(+):Treg ratios, and increased memory T cells while decreasing naïve T cells. The majority of patients demonstrated these broad T-cell changes, although patients with a partial response or better showed greater maximum effector and helper T-cell increases, elevated antiviral and alloreactive functional responses, and significantly greater increases in T-cell clonality as measured by T-cell receptor (TCR) sequencing. Increased TCR clonality positively correlated with increased CD8(+) PB T-cell counts. Depletion of CD38(+) immunosuppressive cells, which is associated with an increase in T-helper cells, cytotoxic T cells, T-cell functional response, and TCR clonality, represents possible additional mechanisms of action for daratumumab and deserves further exploration