1,721,073 research outputs found
Organic Isothiocyanates as Hydrogen Sulfide Donors
No full textSignificance: Hydrogen sulfide (H2S), the "new entry" in the series of endogenous gasotransmitters, plays a fundamental role in regulating the biological functions of various organs and systems. Consequently, the lack of adequate levels of H2S may represent the etiopathogenetic factor of multiple pathological alterations. In these diseases, the use of H2S donors represents a precious and innovative opportunity. Recent Advances: Natural isothiocyanates (ITCs), sulfur compounds typical of some botanical species, have long been investigated because of their intriguing pharmacological profile. Recently, the ITC moiety has been proposed as a new H2S-donor chemotype (with a l-cysteine-mediated reaction). Based on this recent discovery, we can clearly observe that almost all the effects of natural ITCs can be explained by the H2S release. Consistently, the ITC function was also used as an original H2S-releasing moiety for the design of synthetic H2S donors and original "pharmacological hybrids." Very recently, the chemical mechanism of H2S release, resulting from the reaction between l-cysteine and some ITCs, has been elucidated. Critical Issues: Available literature gives convincing demonstration that H2S is the real player in ITC pharmacology. Further, countless studies have been carried out on natural ITCs, but this versatile moiety has been used only rarely for the design of synthetic H2S donors with optimal drug-like properties. Future Directions: The development of more ITC-based synthetic H2S donors with optimal drug-like properties and selectivity toward specific tissues/pathologies seem to represent a stimulating and indispensable prospect of future experimental activities
Plants and Mushrooms as Possible New Sources of H2S Releasing Sulfur Compounds
Full text linkHydrogen sulfide (H2S), known for many decades exclusively for its toxicity and the smell of rotten eggs, has been re-discovered for its pleiotropic effects at the cardiovascular and non-cardiovascular level. Therefore, great attention is being paid to the discovery of molecules able to release H2S in a smart manner, i.e., slowly and for a long time, thus ensuring the maintenance of its physiological levels and preventing "H2S-poor" diseases. Despite the development of numerous synthetically derived molecules, the observation that plants containing sulfur compounds share the same pharmacological properties as H2S led to the characterization of naturally derived compounds as H2S donors. In this regard, polysulfuric compounds occurring in plants belonging to the Alliaceae family were the first characterized as H2S donors, followed by isothiocyanates derived from vegetables belonging to the Brassicaceae family, and this led us to consider these plants as nutraceutical tools and their daily consumption has been demonstrated to prevent the onset of several diseases. Interestingly, sulfur compounds are also contained in many fungi. In this review, we speculate about the possibility that they may be novel sources of H2S-donors, furnishing new data on the release of H2S from several selected extracts from fungi
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing
Full text linkThe human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models
In Vitro Models of Diabetes: Focus on Diabetic Retinopathy
Full text linkDiabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology
The role of hydrogen sulfide and H2S-donors in myocardial protection against ischemia/reperfusion injury
No full textHydrogen 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 S-sufhydration able to modify proteins such as ion channels. Particular attention was focused on the mitochondrial preservation and on anti-apoptotic mechanisms, and finally even a pro-angiogenesis effect has been described. At the same time, the design, the development and the pharmacological characterization of moieties able to release H2S, employed alone as H2S-donor, or conjugated with another drug in hybrid molecules, led to the production of novel chemical entities in the panorama of cardioprotective drugs
Using hydrogen sulfide to design and develop drugs
No full textHydrogen 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 to exciting pharmacological perspectives for drugs acting on the "H2S system". Areas covered: At the beginning of this manuscript, the authors present the biological roles and mechanisms of action of hydrogen sulfide. The authors then discuss the developments in the modulation of the H2S system via heterogeneous molecules, which behave as sources of exogenous H2S, and are promising drugs for a number of diseases. Expert opinion: The rate of H2S generation, the physicochemical characteristics and the bioavailability greatly affect the overall pharmacological profile of each H2S-releasing compound. Therefore, the development of broad collections of original moieties endowed with heterogeneous rates/mechanisms of H2S-release and a variety of physicochemical, biological and pharmacological features is the most timely and compelling issue in the field of H2S-based drug discovery
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