Ceramide/protein phosphatase 2A axis is engaged in gap junction impairment elicited by PCB153 in liver stem-like progenitor cells.

The widespread environmental pollutant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) is a non-dioxin-like toxicant. It is a potential carcinogen compound able to induce gap junction (GJ) intercellular communication impairment, probably the first non-genomic event leading to tumor promotion. Although PCBs have been known for many years, the molecular mode of PCB153 action is still unclear.

Adiponectin Decreases Gastric Smooth Muscle Cell Excitability in Mice.

Some adipokines known to regulate food intake at a central level can also affect gastrointestinal motor responses. These are recognized to be peripheral signals able to influence feeding behavior as well. In this view, it has been recently observed that adiponectin (ADPN), which seems to have a role in sending satiety signals at the central nervous system level, actually affects the mechanical responses in gastric strips from mice.

Adiponectin affects the mechanical responses in strips from the mouse gastric fundus.

Aim: To investigate whether the adipocytes derived hormone adiponectin (ADPN) affects the mechanical responses in strips from the mouse gastric fundus.

Methods: For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension.

Relaxin influences ileal muscular activity through a dual signaling pathway in mice.

Aim: To investigate the signaling pathways involved in the relaxin (RLX) effects on ileal preparations from mice through mechanical and electrophysiological experiments.

Methods: For mechanical experiments, ileal preparations from female mice were mounted in organ baths containing Krebs-Henseleit solution. The mechanical activity was recorded force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension.

Cortical and spinal conditioned media modify the inward ion currents and excitability and promote differentiation of human striatal primordium.

Human striatal precursor cells (HSPs) isolated from ganglionic eminence may differentiate in electrophysiologically functional excitable neuron-like cells and a number of endogenous molecules such as hormones, neurotransmitters or growth factors can actually regulate neuronal growing and differentiation. The purpose of this research was to assess, by electrophysiological and immunocytochemical analysis, if the type of culture medium could specifically impact on the neuronal differentiation potential of HSPs. Accordingly, HSPs were maintained in different inductive media such as cortical and spinal cord conditioned media, and we estimated the possible changes in the main ion currents, excitability and expression of neuronal markers indicative of neuronal differentiation.

An electrophysiological study on the effects of BDNF and FGF2 on voltage dependent Ca(2+) currents in developing human striatal primordium.

Over the past decades, studies in both Huntington's disease animal models and pilot clinical trials have demonstrated that replacement of degenerated striatum and repair of circuitries by grafting fetal striatal primordium is feasible, safe and may counteract disease progression. However, a better comprehension of striatal ontogenesis is required to assess the fetal graft regenerative potential. During neuronal development, neurotrophins exert pleiotropic actions in regulating cell fate and synaptic plasticity.

Hyponatraemia alters the biophysical properties of neuronal cells independently of osmolarity: a study on Ni(2+) -sensitive current involvement.

What is the central question of this study? Hyponatraemia, an electrolyte disorder encountered in hospitalized patients, can cause neurological symptoms usually attributed to a reduction in plasma osmolarity. Here, we investigated whether low [Na(+) ] per se can cause neuronal changes independent of osmolarity, focusing on involvement of the Na(+) -Ca(2+) exchanger. What is the main finding and its importance? We show that hyponatraemia per se causes alterations of neuronal properties.

Relaxin Affects Smooth Muscle Biophysical Properties and Mechanical Activity of the Female Mouse Colon.

The hormone relaxin (RLX) has been reported to influence gastrointestinal motility in mice. However, at present, nothing is known about the effects of RLX on the biophysical properties of the gastrointestinal smooth muscle cells (SMCs). Other than extending previous knowledge of RLX on colonic motility, the purpose of this study was to investigate the ability of the hormone to induce changes in resting membrane potential (RMP) and on sarcolemmal ion channels of colonic SMCs of mice that are related to its mechanical activity.

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium.

Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors.

Inhibitory effects of relaxin on cardiac fibroblast-to-myofibroblast transition: an electrophysiological study.

What is the central question of this study? Fibroblast-to-myofibroblast transition is a key mechanism in the reparative response to tissue damage, but myofibroblast persistence in the wound leads to fibrosis and organ failure. The role of relaxin as an antifibrotic agent capable of counteracting the acquisition of biophysical features of differentiated myofibroblasts deserves further investigation. What is the main finding and its importance? Electrophysiological analysis showed that relaxin, administered during profibrotic treatment, hyperpolarizes the membrane potential and attenuates delayed rectifier and inwardly rectifying K(+) currents, which usually increase in the transition to myofibroblasts.

Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells.

Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family.

Influence of obestatin on the gastric longitudinal smooth muscle from mice: mechanical and electrophysiological studies.

Obestatin is a hormone released from the stomach deriving from the same peptide precursor as ghrelin. It is known to act as an anorectic hormone decreasing food intake, but contrasting results have been reported about the effects of obestatin on gastrointestinal motility. The aim of the present study was to investigate whether this peptide may act on the gastric longitudinal smooth muscle by using a combined mechanical and electrophysiological approach.

Muscular effects of relaxin on the mouse colon: mechanical and electrophysiological studies.

Relaxin has been reported to influence gastrointestinal motility in mice. However, at present, nothing is known about the effects of relaxin on the electrophysiological properties of the gastrointestinal smooth muscle. In the present experiments relaxin, other than influencing the colonic motility pattern, has been shown to act on cell membrane properties.

Photoactivation of bone marrow mesenchymal stromal cells with diode laser: effects and mechanisms of action.

Mesenchymal stromal cells (MSCs) are a promising cell candidate in tissue engineering and regenerative medicine. Their proliferative potential can be increased by low-level laser irradiation (LLLI), but the mechanisms involved remain to be clarified. With the aim of expanding the therapeutic application of LLLI to MSC therapy, in the present study we investigated the effects of 635 nm diode laser on mouse MSC proliferation and investigated the underlying cellular and molecular mechanisms, focusing the attention on the effects of laser irradiation on Notch-1 signal activation and membrane ion channel modulation.

Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell.

Metabolic pathologies mainly originate from adipose tissue (AT) dysfunctions. AT differences are associated with fat-depot anatomic distribution in subcutaneous (SAT) and visceral omental (VAT) pads. We address the question whether the functional differences between the two compartments may be present early in the adipose stem cell (ASC) instead of being restricted to the mature adipocytes.

Combined effects of melatonin and all-trans retinoic acid and somatostatin on breast cancer cell proliferation and death: molecular basis for the anticancer effect of these molecules.

Melatonin has been shown to inhibit breast cancer cell growth in numerous studies. However, our understanding of the therapeutic effects of this hormone is still marginal and there is little information concerning its combination with other antitumor agents to achieve additional potential benefits. All-trans retinoic acids or somatostatin have been used in combination with melatonin in several pre-clinical and clinical trials, but they have never been combined altogether as an anti-breast cancer treatment.

Muscular effects of orexin A on the mouse duodenum: mechanical and electrophysiological studies.

Orexin A (OXA) has been reported to influence gastrointestinal motility, acting at both central and peripheral neural levels. The aim of the present study was to evaluate whether OXA also exerts direct effects on the duodenal smooth muscle. The possible mechanism of action involved was investigated by employing a combined mechanical and electrophysiological approach.

Relaxin promotes growth and maturation of mouse neonatal cardiomyocytes in vitro: clues for cardiac regeneration.

The demonstration that the adult heart contains myocardial progenitor cells which can be recruited in an attempt to replace the injured myocardium has sparkled interest towards novel molecules capable of improving the differentiation of these cells. In this context, the peptide hormone relaxin (RLX), recently validated as a cardiovascular hormone, is a promising candidate. This study was designed to test the hypothesis that RLX may promote the growth and maturation of mouse neonatal immature cardiomyocytes in primary culture.

Effects of S1P on skeletal muscle repair/regeneration during eccentric contraction.

Skeletal muscle regeneration is severely compromised in the case of extended damage. The current challenge is to find factors capable of limiting muscle degeneration and/or potentiating the inherent regenerative program mediated by a specific type of myoblastic cells, the satellite cells. Recent studies from our groups and others have shown that the bioactive lipid, sphingosine 1-phosphate (S1P), promotes myoblast differentiation and exerts a trophic action on denervated skeletal muscle fibres.

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis.

We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel activity with Cx43 expression/function, investigating the involvement of the Ca(2+)-sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P.

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model.

Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.

A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility.

To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties and electrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation: 1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lost nerve influence, playing a key role in modifying the gene expression of denervated muscle.

Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue.

Adipose tissue is a dynamic endocrine organ with a central role in metabolism regulation. Functional differences in adipose tissue seem associated with the regional distribution of fat depots, in particular in subcutaneous and visceral omental pads. Here, we report for the first time the isolation of human adipose-derived adult stem cells from visceral omental and subcutaneous fat (V-ASCs and S-ASCs, respectively) from the same subject.

Skeletal myoblasts overexpressing relaxin improve differentiation and communication of primary murine cardiomyocyte cell cultures.

The possibility that resident myocardial progenitor cells may be re-activated by transplantation of exogenous stem cells into the post-infarcted heart has been suggested as a possible mechanism to explain the heart's functional improvement after stem cell therapy. Here we studied whether differentiation of mouse neonatal immature cardiomyocytes in vitro was influenced by mouse skeletal myoblasts C2C12, wild type or engineered to secrete the cardiotropic hormone relaxin. The cultured cardiomyocytes formed spontaneously beating clusters and temporally exhibited cardiac immunophenotypical (cKit, atrial natriuretic peptide, troponin T, connexin-43, HCN4) and electrical features (inward voltage-dependent Na(+), T- and L-type Ca(2+) currents, outward and inward K(+) currents, I(f) pacemaker current).

Prominent role of relaxin in improving postinfarction heart remodeling.

Stem cell transplantation is a promising approach for treatment of the postinfarcted heart and prevention of deleterious cardiac remodeling and heart failure. We explored this issue by transplanting mouse C2C12 myoblasts, genetically engineered to express enhanced green fluorescent protein (eGFP) or eGFP and relaxin (eGFP/RLX), into swine with chronic myocardial infarction. One month later, C2C12 myoblasts selectively settled in the ischemic scar around blood vessels, showing an activated endothelium (ICAM-1 and VCAM positive).