From bench to bedside: in vitro and in vivo evaluation of a neonate-focused nebulized surfactant delivery strategy.

Background: Non-invasive delivery of nebulized surfactant has been a neonatology long-pursued goal. Nevertheless, the clinical efficacy of nebulized surfactant remains inconclusive, in part, due to the great technical challenges of depositing nebulized drugs in the lungs of preterm infants. The aim of this study was to investigate the feasibility of delivering nebulized surfactant (poractant alfa) in vitro and in vivo with an adapted, neonate-tailored aerosol delivery strategy.

The Association With Two Different Arbuscular Mycorrhizal Fungi Differently Affects Water Stress Tolerance in Tomato.

Arbuscular mycorrhizal (AM) fungi are very widespread, forming symbiotic associations with ∼80% of land plant species, including almost all crop plants. These fungi are considered of great interest for their use as biofertilizer in low-input and organic agriculture. In addition to an improvement in plant nutrition, AM fungi have been reported to enhance plant tolerance to important abiotic and biotic environmental conditions, especially to a reduced availability of resources.

Mass spectrometry and metallomics: A general protocol to assess stability of metallodrug-protein adducts in bottom-up MS experiments.

The bottom-up mass spectrometry approach is today one of the best tools of Metallomics to characterize the binding of metal-based drugs to proteins. Yet, the stability of metal-protein coordination bonds along the whole process may be a critical issue. This led us to build up a general protocol to test metallodrug-protein adduct stability under the typical conditions of the filter-aided sample preparation (FASP)/bottom-up procedure, ranging from the analysis of solutions containing metal-protein adducts to tandem mass spectrometry experiments.

TRPA1 Mediates Aromatase Inhibitor-Evoked Pain by the Aromatase Substrate Androstenedione.

Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, as the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of patients, we hypothesized that additional factors may cooperate to induce AIMSS. Here we report that the aromatase substrate androstenedione, unique among several steroid hormones, targeted TRPA1 in peptidergic primary sensory neurons in rodent and human cells expressing the native or recombinant channel.

NLRP3 inflammasome as a target of berberine in experimental murine liver injury: interference with P2X7 signalling.

Berberine (BRB) is commonly used in herbal medicine, but its mechanisms of action are poorly understood. In the present study, we tested BRB in steatohepatitis induced by a methionine- and choline-deficient (MCD) diet, in acute acetaminophen intoxication and in cultured murine macrophages. BRB markedly improved parameters of liver injury and necroinflammation induced by the MCD diet, although increased mortality was observed by mechanisms independent of bacterial infections or plasma levels of BRB.

Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1.

Use of aromatase inhibitors (AIs), exemestane, letrozole and anastrozole, for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. The electrophilic nature of AIs suggests that they may target the transient receptor potential ankyrin 1 (TRPA1) channel, a major pathway in pain transmission and neurogenic inflammation. AIs evoke TRPA1-mediated calcium response and current in rodent nociceptors and human cells expressing the recombinant channel.

Impact of drug administration route on drug delivery and distribution into the lung: an imaging mass spectrometry approach.

During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes.

A proteomic investigation of soluble olfactory proteins in Anopheles gambiae.

Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are small soluble polypeptides that bind semiochemicals in the lymph of insect chemosensilla. In the genome of Anopheles gambiae, 66 genes encode OBPs and 8 encode CSPs. Here we monitored their expression through classical proteomics (2D gel-MS analysis) and a shotgun approach.

Top-down sequencing of Apis dorsata apamin by MALDI-TOF MS and evidence of its inactivity against microorganisms.

Apis mellifera venom is one of the best characterized venoms among Hymenoptera, yet relatively little is known about venom belonging to other species in the genus Apis. Melittin, one of the most important bioactive peptides, has been isolated and characterized in A. mellifera, Apis cerana, Apis dorsata and Apis florea, while apamin has been only characterized in A.

Effect of IR laser on myoblasts: a proteomic study.

Laser therapy is used in physical medicine and rehabilitation to accelerate muscle recovery and in sports medicine to prevent damages produced by metabolic disturbances and inflammatory reactions after heavy exercise. The aim of this research was to get insight into possible benefits deriving from the application of an advanced IR laser system to counteract deficits of muscle energy metabolism and stimulate the recovery of hypotrophic tissue. We studied the effect of IR laser treatment on proliferation, differentiation, cytoskeleton organization and global protein expression in C2C12 myoblasts.

Three-dimensional molecular reconstruction of rat heart with mass spectrometry imaging.

Cardiovascular diseases are the world's number one cause of death, accounting for 17.1 million deaths a year. New high-resolution molecular and structural imaging strategies are needed to understand underlying pathophysiological mechanism.

In situ imaging of honeybee (Apis mellifera) venom components from aqueous and aluminum hydroxide-adsorbed venom immunotherapy preparations.

Background: Treatment with aqueous and aluminum hydroxide (Al[OH](3))-adsorbed purified honeybee (Apis mellifera) venom (HBV) preparations can reduce the incidence of side effects associated with venom immunotherapy.

Objective: The aim of the present study was to assess these purified HBV immunotherapy preparations in situ.

Methods: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize the distribution of HBV components.

The double nature of 1,5-diaminonaphthalene as matrix-assisted laser desorption/ionization matrix: some experimental evidence of the protonation and reduction mechanisms.

1,5-Diaminonaphthalene (DAN) has been described as an interesting and effective matrix for matrix-assisted laser desorption/ionization (MALDI) experiments in positive ion mode, being able to activate in-source decomposition phenomena and, when employed for the analysis of proteins containing disulphide bridge(s), being able to activate reduction processes, resulting in disulphide bridge cleavage. The mechanisms of the DAN reactivity have been studied in detail, and the results indicate that the reduction properties of the matrix are of a radical nature. In the present study the structure of the reactive species produced by DAN, responsible for its reductive properties, has been investigated by accurate mass measurements and tandem mass spectrometry (MS/MS) experiments.

Structural and solution chemistry, protein binding and antiproliferative profiles of gold(I)/(III) complexes bearing the saccharinato ligand.

A series of new gold(I) and gold(III) complexes based on the saccharinate (sac) ligand, namely M[Au(sac)(2)] (with M being Na(+), K(+) or NH(4)(+)), [(PTA)Au(sac)], K[Au(sac)(3)Cl] and Na[Au(sac)(4)], were synthesized and characterized, and some aspects of their biological profile investigated. Spectrophotometric analysis revealed that these gold compounds, upon dissolution in aqueous media, at physiological pH, manifest a rather favourable balance between stability and reactivity. Their reactions with the model proteins cytochrome c and lysozyme were monitored by mass spectrometry to predict their likely interactions with protein targets.

Vitamin D3 quantification in a cod liver oil-based supplement.

A reliable, accurate and reproducible method to quantify vitamin D3 (Vit. D3) in oily dietary supplements was developed after three Vit. D3 intoxications were diagnosed as reasonably resulting from a dietary administration of a cod liver oil based supplement.

Odorant-binding proteins and chemosensory proteins in pheromone detection and release in the silkmoth Bombyx mori.

The genome of the silkmoth Bombyx mori contains 44 genes encoding odorant-binding proteins (OBPs) and 20 encoding chemosensory proteins (CSPs). In this work, we used a proteomic approach to investigate the expression of proteins of both classes in the antennae of adults and in the female pheromone glands. The most abundant proteins found in the antennae were the 4 OBPs (PBP, GOBP1, GOBP2, and ABP) and the 2 CSPs (CSP1 and CSP2) previously identified and characterized.

Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool.

The NAD rescue pathway consists of two enzymatic steps operated by nicotinamide phosphoribosyltransferase (Nampt) and nicotinamide mononucleotide adenylyltransferases. Recently, the potent Nampt inhibitor FK866 has been identified and evaluated in clinical trials against cancer. Yet, how Nampt inhibition affects NAD contents and bioenergetics is in part obscure.

Rapid assay of rufinamide in dried blood spots by a new liquid chromatography-tandem mass spectrometric method.

Rufinamide (RUF) is a new antiepileptic drug with efficacy in several types of seizures. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate RUF levels during treatment. Therapeutic drug monitoring of RUF could be useful in routine clinical practice.

Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus-transgenic mice by peroxisome proliferator-activated receptor gamma-independent regulation of nucleophosmin.

Unlabelled: Antidiabetic thiazolidinediones (TZD) have in vitro antiproliferative effect in epithelial cancers, including hepatocellular carcinoma (HCC). The effective anticancer properties and the underlying molecular mechanisms of these drugs in vivo remain unclear. In addition, the primary biological target of TZD, the ligand-dependent transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), is up-regulated in HCC and seems to provide tumor-promoting responses.

Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed on melanoma cells.

Immunotherapy of tumors and of melanoma in particular has a long history, and recently this therapeutic approach found a reliable scientific rationale. This biological therapy aims to teach the patient's immune system to recognize the antigens expressed on tumor cells and destroy them, leaving normal cells intact. The success of this therapy highly depends on the selection of target antigens that are essential for tumors growth and progression.

Mapping the expression of soluble olfactory proteins in the honeybee.

Chemical communication in insects is mediated by soluble binding proteins, belonging to two large families, Odorant-binding Proteins (OBPs) and Chemosensory Proteins (CSPs). Recently, evidence has been provided that OBPs are involved in recognition of chemical stimuli. We therefore decided to investigate the expression of OBPs and CSPs in the honeybee at the protein level, using a proteomic approach.

CSF proteomic analysis in patients with normal pressure hydrocephalus selected for the shunt: CSF biomarkers of response to surgical treatment.

The aim of our pilot study was to investigate, by a proteomic approach, the expressed differences in cerebrospinal fluid (CSF) protein patterns in order to aid in the diagnosis and treatment of normal pressure hydrocephalus (NPH). Seventeen patients with NPH, selected by Intracranial-Pressure monitoring (ICPmo), underwent implantation of a shunt and after 6 months were clinically re-evaluated. Thirteen patients improved, whereas four did not.