The cellular protrusions for inter-cellular material transfer: similarities between filopodia, cytonemes, tunneling nanotubes, viruses, and extracellular vesicles.

Extracellular vesicles (EVs) are crucial for transferring bioactive materials between cells and play vital roles in both health and diseases. Cellular protrusions, including filopodia and microvilli, are generated by the bending of the plasma membrane and are considered to be rigid structures facilitating various cellular functions, such as cell migration, adhesion, and environment sensing. Compelling evidence suggests that these protrusions are dynamic and flexible structures that can serve as sources of a new class of EVs, highlighting the unique role they play in intercellular material transfer.

Extracellular vesicles released by keratinocytes regulate melanosome maturation, melanocyte dendricity, and pigment transfer.

Extracellular vesicles (EVs) facilitate the transfer of proteins, lipids, and genetic material between cells and are recognized as an additional mechanism for sustaining intercellular communication. In the epidermis, the communication between melanocytes and keratinocytes is tightly regulated to warrant skin pigmentation. Melanocytes synthesize the melanin pigment in melanosomes that are transported along the dendrites prior to the transfer of melanin pigment to keratinocytes.

Microvilli-derived extracellular vesicles carry Hedgehog morphogenic signals for Drosophila wing imaginal disc development.

Morphogens are secreted molecules that regulate and coordinate major developmental processes, such as cell differentiation and tissue morphogenesis. Depending on the mechanisms of secretion and the nature of their carriers, morphogens act at short and long range. We investigated the paradigmatic long-range activity of Hedgehog (Hh), a well-known morphogen, and its contribution to the growth and patterning of the Drosophila wing imaginal disc.

Translating the Symptom Screening in Pediatrics Tool (SSPedi) into Argentinian Spanish for paediatric patients receiving cancer treatments, and evaluating understandability and cultural relevance in a multiple-phase descriptive study.

Objectives: To translate a symptom screening tool developed for paediatric patients receiving cancer therapies called Symptom Screening in Pediatrics Tool (SSPedi) into Argentinian Spanish and to evaluate the understandability and cultural relevance of the translated version of SSPedi among children with cancer and paediatric haematopoietic stem cell transplant (HSCT) recipients.

Methods: We conducted a multiphase, descriptive study to translate SSPedi into Argentinian Spanish. Using two translators, forward and backward translations were performed.

Centrosome amplification mediates small extracellular vesicle secretion via lysosome disruption.

Bidirectional communication between cells and their surrounding environment is critical in both normal and pathological settings. Extracellular vesicles (EVs), which facilitate the horizontal transfer of molecules between cells, are recognized as an important constituent of cell-cell communication. In cancer, alterations in EV secretion contribute to the growth and metastasis of tumor cells.

The GTPase Rab8 differentially controls the long- and short-range activity of the Hedgehog morphogen gradient by regulating Hedgehog apico-basal distribution.

The Hedgehog (Hh) morphogen gradient is required for patterning during metazoan development, yet the mechanisms involved in Hh apical and basolateral release and how this influences short- and long-range target induction are poorly understood. We found that depletion of the GTPase Rab8 in Hh-producing cells induces an imbalance between the level of apically and laterally released Hh. This leads to non-cell-autonomous differential effects on the expression of Hh target genes, namely an increase in its short-range targets and a concomitant decrease in long-range targets.

Translating the Symptom Screening in Paediatrics Tool (SSPedi) into North American Spanish and Among Spanish-speaking children receiving cancer treatments: evaluating understandability and cultural relevance in a multiple-phase descriptive study.

Objectives: Symptom screening is important to achieving symptom control. Symptom Screening in Paediatrics Tool (SSPedi) is validated for English-speaking children. Objectives were to translate SSPedi into Spanish, and to evaluate the understandability and cultural relevance of the translated version among Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplant recipients.

Shedding light on the cell biology of extracellular vesicles.

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.

Endocytosis of Hedgehog through dispatched regulates long-range signaling.

The proteins of the Hedgehog (Hh) family are secreted proteins exerting short- and long-range control over various cell fates in developmental patterning. The Hh gradient in Drosophila wing imaginal discs consists of apical and basolateral secreted pools, but the mechanisms governing the overall establishment of the gradient remain unclear. We investigated the relative contributions of endocytosis and recycling to control the Hh gradient.

The ESCRT machinery regulates the secretion and long-range activity of Hedgehog.

The conserved family of Hedgehog (Hh) proteins acts as short- and long-range secreted morphogens, controlling tissue patterning and differentiation during embryonic development. Mature Hh carries hydrophobic palmitic acid and cholesterol modifications essential for its extracellular spreading. Various extracellular transportation mechanisms for Hh have been suggested, but the pathways actually used for Hh secretion and transport in vivo remain unclear.

A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

Hedgehog (Hh) proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development.

The full-length unprocessed hedgehog protein is an active signaling molecule.

The hedgehog (HH) family of ligands plays an important instructional role in metazoan development. HH proteins are initially produced as approximately 45-kDa full-length proteins, which undergo an intramolecular cleavage to generate an amino-terminal product that subsequently becomes cholesterol-modified (HH-Np). It is well accepted that this cholesterol-modified amino-terminal cleavage product is responsible for all HH-dependent signaling events.

Soluble nickel inhibits HIF-prolyl-hydroxylases creating persistent hypoxic signaling in A549 cells.

Soluble nickel compounds are carcinogenic to humans although the mechanism by which they cause cancer remains unclear. One major consequence of exposure to nickel is the stabilization of hypoxia inducible factor-1alpha (HIF-1alpha), a protein known to be overexpressed in a variety of cancers. In this study, we report a persistent stabilization of HIF-1alpha by nickel chloride up to 72 h after the removal of nickel from the culture media.

Soluble nickel interferes with cellular iron homeostasis.

Soluble nickel compounds are likely human carcinogens. The mechanism by which soluble nickel may contribute to carcinogenesis is unclear, though several hypotheses have been proposed. Here we verify the ability of nickel to enter the cell via the divalent metal ion transporter 1 (DMT1) and disturb cellular iron homeostasis.

Analysis of the hypoxia-sensing pathway in Drosophila melanogaster.

The mechanism by which hypoxia induces gene transcription involves the inhibition of HIF-1alpha (hypoxia-inducible factor-1 alpha subunit) PHD (prolyl hydroxylase) activity, which prevents the VHL (von Hippel-Lindau)-dependent targeting of HIF-1alpha to the ubiquitin/proteasome pathway. HIF-1alpha thus accumulates and promotes gene transcription. In the present study, first we provide direct biochemical evidence for the presence of a conserved hypoxic signalling pathway in Drosophila melanogaster.

Hypoxia up-regulates prolyl hydroxylase activity: a feedback mechanism that limits HIF-1 responses during reoxygenation.

The mechanism by which hypoxia induces gene transcription is now well established. Hypoxia reduces activity of prolyl hydroxylases (PHD) that hydroxylate specific proline residues in the oxygen-dependent degradation domain (ODD) of hypoxia-inducible factor-1alpha (HIF-1alpha). As a consequence, HIF-1alpha accumulates and promotes hypoxic tolerance by activating gene transcription.

Cyclosporin A prevents the hypoxic adaptation by activating hypoxia-inducible factor-1alpha Pro-564 hydroxylation.

The mechanism by which hypoxia induces gene transcription involves the inhibition of hypoxia-inducible factor (HIF)-1alpha prolyl hydroxylase activity, which prevents von Hippel-Lindau (vHL)-dependent targeting of HIF-1alpha to the ubiquitin-proteasome pathway. HIF-1alpha is stabilized, translocates to the nucleus, interacts with hypoxia-responsive elements, and promotes the activation of target genes. This report shows that cyclosporin A (CsA) interferes with the hypoxic signaling cascade in C6 glioma cells.

A chemically modified dextran inhibits smooth muscle cell growth in vitro and intimal in stent hyperplasia in vivo.

Purpose: Intimal smooth muscle cell (SMC) hyperplasia is a main component of the arterial wall response to injury. We have investigated the capacity of a water-soluble nonanticoagulant functionalized dextran (E9) in inhibition of SMC growth in vitro and in vivo.

Methods: E9 was obtained with chemical substitutions with anionic and hydrophobic groups on the dextran backbone.

Heparin and non-heparin-like dextrans differentially modulate endothelial cell proliferation: in vitro evaluation with soluble and crosslinked polysaccharide matrices.

Proliferation of endothelial cells (ECs) is a cellular step of particular importance for implanted cardiovascular biomaterials. Heparin and some synthetic water-soluble non-anticoagulant polysaccharides derived from dextran and bearing anionic carboxymethyl and hydrophobic benzylamine groups were first investigated for their effects on EC proliferation in vitro. The results assessed by cell counting, 3H-thymidine uptake, and flow cytometry analysis, showed that the derivatized dextran-bearing hydrophobic groups stimulated the EC growth in the presence of serum, whereas native dextran or dextran-bearing anionic carboxymethyl groups were inactive and heparin was slightly inhibitory.