Erucin exhibits vasorelaxing effects and antihypertensive activity by H S-releasing properties.

Background And Purpose: Hydrogen sulfide (H S)-releasing agents are viewed as potential antihypertensive drugs. Recently, natural isothiocyanates emerged as original H S-donor agents. Among them, erucin, present in some edible cruciferous plants, shows suitable H S-releasing properties and features of "druggability.

Circulating cell-free microRNAs in cutaneous melanoma staging and recurrence or survival prognosis.

Cutaneous melanoma is a skin cancer with increasing incidence. Identification of novel clinical biomarkers able to detect the stage of disease and suggest prognosis could improve treatment and outcome for melanoma patients. Cell-free microRNAs (cf-miRNAs) are the circulating copies of short non-coding RNAs involved in gene expression regulation.

Phosphorylation of AKT and ERK1/2 and mutations of PIK3CA and PTEN are predictive of breast cancer cell sensitivity to everolimus in vitro.

Background: Everolimus is the hydroxyethyl derivative of sirolimus and a strong inhibitor of mammalian target of rapamycin (mTOR). This drug has immunosuppressive and anticancer activities and the present in vitro study was aimed at identifying the cellular and molecular profiles of breast cancer cells predictive of sensitivity to everolimus.

Materials And Methods: MCF-7, T-47D, ZR-75-1, CAMA-1, HCC-1500 and MCF-10A cells were used and viability was assessed using WST-1 dye.

The Role of Hydrogen Sulfide and H2S-donors in Myocardial Protection Against Ischemia/Reperfusion Injury.

Hydrogen sulfide (H2S), previously known only as a toxic agent, in the last decades has been recognized as an important endogenous gasotransmitter, playing a key role in the homeostasis of the cardiovascular system. In the last years, the growing evidence about a protective role exhibited by H2S against myocardial ischemia/reperfusion (I/R), led to an increasing interest for the possible mechanism of action accounting for the H2S cardioprotective effect, and to the discovery of the involvement of several targets. Currently, many mechanisms of action have been proposed and verified through in vitro and in vivo models of I/R injury, such as the anti-inflammatory or the anti-oxidant ones, or mechanisms of Ssufhydration able to modify proteins such as ion channels.

The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs.

In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects.

Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs.

Background: Mitochondria play a central role in ATP-generating processes. Indeed, in mammalian tissues, up to 90% of ATP is generated by mitochondria through the process of oxidative phosphorylation; furthermore, mitochondria are involved in multiple signal transduction pathways. A rapidly expanding body of literature has confirmed that mitochondria play a pivotal role in apoptosis, cardio- and neuro-protection, and various neurodegenerative disorders, ranging from Parkinson's to Alzheimer's disease.

Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol.

Mitochondria play a crucial role in the cell fate; in particular, reducing the accumulation of calcium in the mitochondrial matrix offers cardioprotection. This affect is achieved by a mild depolarization of the mitochondrial membrane potential, which prevents the assembly and opening of the mitochondrial permeability transition pore. For this reason, mitochondria are an attractive target for pharmacological interventions that prevent ischaemia/reperfusion injury.

Iminothioethers as Hydrogen Sulfide Donors: From the Gasotransmitter Release to the Vascular Effects.

The gasotransmitter hydrogen sulfide (HS) is an important tuner of the cardiovascular homeostasis, and its deficiency is etiologically associated with a number of cardiovascular diseases. Therefore, the research of original moieties able to release HS represents a timely issue for drug discovery. In this work, we developed a collection of iminothioethers (ITEs), exhibiting HS-releasing properties and producing vasorelaxing effects on rat aortic rings.

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma.

Melanoma is a devastating disease with few therapeutic options in the advanced stage and with the urgent need of reliable biomarkers for early detection. In this context, circulating microRNAs are raising great interest as diagnostic biomarkers. We analyzed the expression profiles of 21 selected microRNAs in plasma samples from melanoma patients and healthy donors to identify potential diagnostic biomarkers.

Cholinesterase-like organocatalysis by imidazole and imidazole-bearing molecules.

Organocatalysis, which is mostly explored for its new potential industrial applications, also represents a chemical event involved in endogenous processes. In the present study, we provide the first evidence that imidazole and imidazole derivatives have cholinesterase-like properties since they can accelerate the hydrolysis of acetylthiocholine and propionylthiocholine in a concentration-dependent manner. The natural imidazole-containing molecules as L-histidine and histamine show a catalytic activity, comparable to that of imidazole itself, whereas synthetic molecules, as cimetidine and clonidine, were less active.

The Citrus Flavanone Naringenin Produces Cardioprotective Effects in Hearts from 1 Year Old Rat, through Activation of mitoBK Channels.

Incidence of cardiovascular disorders increases with age, because of a dramatic fall of endogenous self-defense mechanisms and increased vulnerability of myocardium. Conversely, the effectiveness of many cardioprotective drugs is blunted in hearts of 1 year old rat. The Citrus flavanone naringenin (NAR) was reported to promote cardioprotective effects against ischemia/reperfusion (I/R) injury, through the activation of mitochondrial large conductance calcium-activated potassium channel (mitoBK).

Tumor-promoting effects of cannabinoid receptor type 1 in human melanoma cells.

The role of endocannabinoid system in melanoma development and progression is actually not fully understood. This study was aimed at clarifying whether cannabinoid-type 1 (CB1) receptor may function as tumor-promoting or -suppressing signal in human cutaneous melanoma. CB1 receptor expression was measured in human melanoma cell lines by real-time PCR.

The novel HS-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia/reperfusion injury through activation of mitoK channels and reduction of oxidative stress.

The endogenous gasotransmitter hydrogen sulphide (HS) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, HS exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning", through activation of mitochondrial potassium channels, reduction of oxidative stress, activation of the endogenous "anti-oxidant machinery" and limitation of inflammatory responses. Accordingly, HS-donors, i.

Application of a pharmacokinetic/pharmacogenetic approach to assess the nicotine metabolic profile of smokers in the real-life setting.

The nicotine metabolite ratio, i.e., the ratio 3-hydroxycotinine/cotinine, is used to assess the nicotine metabolic status and has been proven to predict the response to smoking cessation treatments in randomized clinical trials.

Voltage-operated potassium (Kv) channels contribute to endothelium-dependent vasorelaxation of carvacrol on rat aorta.

Objectives: Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved.

Methods: This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings.

Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells.

Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells.

Expression and function of Kv7.4 channels in rat cardiac mitochondria: possible targets for cardioprotection.

Aims: Plasmalemmal Kv7.1 (KCNQ1) channels are critical players in cardiac excitability; however, little is known on the functional role of additional Kv7 family members (Kv7.2-5) in cardiac cells.

Using hydrogen sulfide to design and develop drugs.

Introduction: Hydrogen sulfide (H2S) is an endogenous gasotransmitter, involved in the regulation of several biological functions. Conversely, impaired biosynthesis of H2S is associated with important diseases. This paves the way for exciting pharmacological perspectives for drugs acting on the 'H2S system'.

Design and synthesis of 2-oxindole based multi-targeted inhibitors of PDK1/Akt signaling pathway for the treatment of glioblastoma multiforme.

Aggressive behavior and diffuse infiltrative growth are the main features of Glioblastoma multiforme (GBM), together with the high degree of resistance and recurrence. Evidence indicate that GBM-derived stem cells (GSCs), endowed with unlimited proliferative potential, play a critical role in tumor development and maintenance. Among the many signaling pathways involved in maintaining GSC stemness, tumorigenic potential, and anti-apoptotic properties, the PDK1/Akt pathway is a challenging target to develop new potential agents able to affect GBM resistance to chemotherapy.

Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells.

Aim: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells.

Materials And Methods: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools included analyses of cell viability, gene expression, cell-cycle progression, annexin V reactivity and internucleosomal DNA fragmentation.

Salbutamol inhibits RhoA activation in normal but not in desensitized bronchial smooth muscle cells.

Objective: This study was aimed at investigating whether the β2 -adrenoceptor agonist, salbutamol, could modulate RhoA activation in normal and homologously desensitized bronchial smooth muscle cells (BSMC).

Methods: Serum-starved BSMCs were stimulated with the Rho-activating compound calpeptin in the presence or absence of salbutamol, the Epac activator, 8-pCPT-2'-O-Me-cAMP, or the site-selective activator of cAMP-dependent protein kinase A (PKA), 6-Bnz-cAMP. Activated RhoA was assessed by immunocytochemical detection and by RhoA G-LISA assay.

Inhibitors of the renal outer medullary potassium channel: a patent review.

Introduction: Hypertension represents a substantial cardiovascular risk factor. Among anti-hypertensive drugs, diuretics play an important role. Nevertheless, they present adverse effects such as hypokalemia or hyperkalemia.

AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells.

Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist with off-target antitumor activity against pancreatic and colon cancer cells. The current study aimed to characterize the in-vitro antimelanoma activity of AM251.

Synthesis and evaluation of multi-functional NO-donor/insulin-secretagogue derivatives for the treatment of type II diabetes and its cardiovascular complications.

Although there is a significant effort in the discovery of effective therapies to contrast both the pathological endocrine and metabolic aspects of diabetes and the endothelial dysfunction associated with this disease, no hypoglycemic drug has been proven to defeat the cardiovascular complications associated with type II diabetes. The aim of this research was to design new compounds exhibiting a double profile of hypoglycemic agents/NO-donors. The synthesis of molecules obtained by the conjunction of NO-donor moieties with two oral insulin-secretagogue drugs (repaglinide and nateglinide) was reported.

Theranostic properties of a survivin-directed molecular beacon in human melanoma cells.

Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB) that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells.