1,720,987 research outputs found
Pharmacological modulation of the hydrogen sulfide (H2S) system by dietary H2S-donors: A novel promising strategy in the prevention and treatment of type 2 diabetes mellitus
No full textType 2 diabetes mellitus (T2DM) represents the most common age-related metabolic disorder, and its management is becoming both a health and economic issue worldwide. Moreover, chronic hyperglycemia represents one of the main risk factors for cardiovascular complications. In the last years, the emerging evidence about the role of the endogenous gasotransmitter hydrogen sulfide (H2S) in the pathogenesis and progression of T2DM led to increasing interest in the pharmacological modulation of endogenous “H2S-system”. Indeed, H2S directly contributes to the homeostatic maintenance of blood glucose levels; moreover, it improves impaired angiogenesis and endothelial dysfunction under hyperglycemic conditions. Moreover, H2S promotes significant antioxidant, anti-inflammatory, and antiapoptotic effects, thus preventing hyperglycemia-induced vascular damage, diabetic nephropathy, and cardiomyopathy. Therefore, H2S-releasing molecules represent a promising strategy in both clinical management of T2DM and prevention of macro- and micro-vascular complications associated to hyperglycemia. Recently, growing attention has been focused on dietary organosulfur compounds. Among them, garlic polysulfides and isothiocyanates deriving from Brassicaceae have been recognized as H2S-donors of great pharmacological and nutraceutical interest. Therefore, a better understanding of the therapeutic potential of naturally occurring H2S-donors may pave the way to a more rational use of these nutraceuticals in the modulation of H2S homeostasis in T2DM
A Meta-Analysis of First-Line Treatments for Unresectable Pleural Mesothelioma: Indirect Comparisons from Reconstructed Individual Patient Data of Six Randomized Controlled Trials
No full textBackground: In unresectable pleural mesothelioma, pemetrexed+cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed. Methods: Our objective was to compare, albeit indirectly, the results of randomized controlled trials on overall survival (OS). The IPDfromKM method was employed for reconstruct individual patient data (IPD) from the graphs of Kaplan–Meier curves. Cox statistics was run to estimate hazard ratios (HRs). Results: After a literature search on Medline (via PubMed) and Scopus databases, six randomized controlled trials were identified in which five new treatments (nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin, chemotherapy plus pembrolizumab, ONCOS-102 plus pemetrexed plus cisplatin/carboplatin and cediranib plus pemetrexed+cisplatin with maintenance with cediranib) were evaluated. In five trials, pemetrexed plus cisplatin was the standard of care given to the control arms. Nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin and chemotherapy plus pembrolizumab showed a significantly better OS compared with controls. ONCOS-102 plus pemetrexed plus cisplatin/carboplatin did not significantly improve OS. In contrast, OS worsened with cisplatin alone and with cediranib plus pemetrexed+cisplatin with maintenance with cediranib. Discussion: Our analysis indicates that, in patients with unresectable pleural mesothelioma, three of the five novel treatments provided a significant survival benefit compared with the standard of care. Further research is needed to confirm the OS benefit found in our analysis with some treatments, whereas cisplatin alone and cediranib plus pemetrexed+cisplatin with maintenance with cediranib do not seem to deserve further research
Potential Effects of Natural H2 S-Donors in Hypertension Management
No full textAfter the discovery of hydrogen sulfide (H2 S) in the central nervous system by Abe and Kimura in 1996, the physiopathological role of H2 S has been widely investigated in several systems such as the cardiovascular. In particular, H2 S plays a pivotal role in the control of vascular tone, exhibiting mechanisms of action able to induce vasodilation: for instance, activation of potassium channels (KATP and Kv7) and inhibition of 5-phosphodiesterase (5-PDE). These findings paved the way for the research of natural and synthetic exogenous H2 S-donors (i.e., molecules able to release H2 S) in order to have new tools for the management of hypertension. In this scenario, some natural molecules derived from Alliaceae (i.e., garlic) and Brassicaceae (i.e., rocket or broccoli) botanical families show the profile of slow H2 S-donors able to mimic the endogenous production of this gasotransmitter and therefore can be viewed as interesting potential tools for management of hypertension or prehypertension. In this article, the preclinical and clinical impacts of these natural H2 S-donors on hypertension and vascular integrity have been reviewed in order to give a complete panorama of their potential use for the management of hypertension and related vascular diseases
Regulation of blood pressure by natural sulfur compounds: Focus on their mechanisms of action
No full textNatural sulfur compounds are emerging as therapeutic options for the management of hypertension and prehypertension. They are mainly represented by polysulfides from Alliaceae (i.e., garlic) and isothiocyanates from Brassicaceae (or crucifers). The beneficial cardiovascular effects of these compounds, especially garlic polysulfides, are well known and widely reported both in preclinical and clinical studies. However, only a few authors have linked the ability of natural sulfur compounds to induce vasorelaxation and subsequent antihypertensive effects with their ability to release hydrogen sulfide (H2S) in biological tissue. H2S is an endogenous gasotransmitter involved in vascular tone regulation. Some cardiovascular diseases, such as hypertension, are associated with lower plasma H2S levels. Consequently, exogenous sources of H2S (H2S donors) have been designed and synthesized or identified among secondary plant metabolites as potential therapeutic options. In addition to antioxidant effects due to its chemical properties as a reducing agent, H2S induces vasorelaxation by interacting with a range of molecular targets. The mechanisms of action accounting for H2S-induced vasodilation include opening of vascular potassium channels (such as ATP-sensitive (KATP) and voltage-operated (Kv7) channels), inhibition of 5-phosphodiesterase (5-PDE), and activation of vascular endothelial growth factor receptor-2 (VEGFR-2). These effects may be attributed to H2S-induced S-persulfidation (or S-sulfhydration), which is a posttranslational modification of cysteine residues of many types of proteins resulting in structural and functional alterations (activation/inhibition). Thus, H2S donors, such as natural sulfur compounds, are promising antihypertensive agents with novel mechanisms of action
Natural H2S-donors: A new pharmacological opportunity for the management of overweight and obesity
No full textThe prevalence of overweight and obesity has progressively increased in the last few years, becoming a real threat to healthcare systems. To date, the clinical management of body weight gain is an unmet medical need, as there are few approved anti-obesity drugs and most require an extensive monitoring and vigilance due to risk of adverse effects and poor patient adherence/persistence. Growing evidence has shown that the gasotransmitter hydrogen sulfide (H2S) and, therefore, H2S-donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H2S-donors are plants from the Alliaceae (garlic and onion), Brassicaceae (e.g., broccoli, cabbage, and wasabi), and Moringaceae botanical families. In particular, polysulfides and isothiocyanates, which slowly release H2S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H2S in regulating adipose tissue function and the potential efficacy of natural H2S-donors in animal models of overweight/obesity, with a final focus on the preliminary results from clinical trials. We conclude that organosulfur-containing plants and their extracts could be used before or in combination with conventional anti-obesity agents to improve treatment efficacy and reduce inflammation in obesogenic conditions. However, further high-quality studies are needed to firmly establish their clinical efficacy
Adherence to Oral Antidiabetic Drugs in Patients with Type 2 Diabetes: Systematic Review and Meta-Analysis
Full text linkPoor adherence to oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) can lead to therapy failure and risk of complications. The aim of this study was to produce an adherence proportion to OADs and estimate the association between good adherence and good glycemic control in patients with T2D. We searched in MEDLINE, Scopus, and CENTRAL databases to find observational studies on therapeutic adherence in OAD users. We calculated the proportion of adherent patients to the total number of participants for each study and pooled study-specific adherence proportions using random effect models with Freeman–Tukey transformation. We also calculated the odds ratio (OR) of having good glycemic control and good adherence and pooled study-specific OR with the generic inverse variance method. A total of 156 studies (10,041,928 patients) were included in the systematic review and meta-analysis. The pooled proportion of adherent patients was 54% (95% confidence interval, CI: 51–58%). We observed a significant association between good glycemic control and good adherence (OR: 1.33; 95% CI: 1.17–1.51). This study demonstrated that adherence to OADs in patients with T2D is sub-optimal. Improving therapeutic adherence through health-promoting programs and prescription of personalized therapies could be an effective strategy to reduce the risk of complications
Transsulfuration Pathway Products and H2S-Donors in Hyperhomocysteinemia: Potential Strategies Beyond Folic Acid
No full textThe transsulfuration pathway plays a central role in the regulation of sulfur metabolism and contributes to the maintenance of cellular homeostasis. Starting from homocysteine, a sulfur-containing amino acid derived from methionine via the methionine cycle, this metabolic pathway supports the biosynthesis of cysteine and other downstream products, such as taurine, serine, reduced glutathione and the gasotransmitter hydrogen sulfide (H2S). The most common disruption of this pathway leads to hyperhomocysteinemia (HHcy), a well-known risk factor for the development of cardiometabolic diseases and other pathological conditions. In this context, identifying effective pharmacological strategies is crucial. Based on both preclinical and clinical evidence, this review provides an updated overview on the role of folates in restoring transsulfuration balance in HHcy and explores the potential effects of downstream products (such as serine, taurine, and precursors of glutathione) under HHcy conditions. Finally, it examines the pharmacological properties of H2S-donors in cultured cells exposed to HHcy and in animal models of HHcy. This summary of the literature offers new perspectives for the treatment of HHcy and the prevention of its associated multiorgan complications
Hydrogen sulfide: The hidden player of isothiocyanates pharmacology
No full textHydrogen sulfide (H 2 S) is an endogenous gasotransmitter that exhibits a plethora of beneficial effects in numerous systems (i.e. cardiovascular system and central nervous system). In particular, H 2 S promotes anti-inflammatory, antioxidant, anti-hypertensive, and cardioprotective properties, thus playing a crucial role in maintaining tissue homeostasis. Accordingly, an impairment in the biosynthesis of H 2 S has been described in the etiopathogenesis of many pathological conditions. Therefore, to ensure a "physiological" balance in the endogenous levels of H 2 S through H 2 S-donors represents an intriguing pharmacological strategy to prevent and/or treat several "H 2 S-poor" pathologies. Among H 2 S-releasing moieties, isothiocyanates (ITCs) have been recently recognized as "smart" H 2 S-donors, as they show a long-lasting and thiol-dependent H 2 S release. Accordingly, both natural and synthetic ITCs promote antioxidant, anti-inflammatory, antiviral, cardioprotective, anticancer, and anti-nociceptive properties. This impressive overlap in the effects exhibited by H 2 S and ITCs also helps for an understanding of their mechanism of action, as they modulate the same intracellular signaling pathways mainly through S-sulfhydration reactions. Finally, both H 2 S and ITCs show a peculiar dualism in their effects, promoting beneficial properties at low concentrations and toxic effects at high doses. This opposite behavior (known as "hormesis") further suggests that H 2 S plays a crucial role in the health-promoting effects of structurally heterogeneous ITCs, "unmasking" the hidden player in the isothiocyanate pharmacology
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
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