Cysteine-10 on 17 β-Hydroxysteroid dehydrogenase 1 has stabilizing interactions in the cofactor binding region and renders sensitivity to sulfhydryl modifying chemicals

17 β-Hydroxysteroid dehydrogenase type 1 (17 β -HSD1) catalyzes the conversion of estrone to the potent estrogen estradiol. 17 β -HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors. Therefore, the enzyme is considered a promising drug target against estrogen-dependent cancers. For the development of novel inhibitors, an improved understanding of the structure-function relationships is essential. In the present study, we examined the role of a cysteine residue, Cys(10), in the Rossmann-fold NADPH binding region, for 17 β -HSD1 function and tested the sensitivity towards sulfhydryl modifying chemicals. 3D structure modeling revealed important interactions of Cys(10) with residues involved in the stabilization of amino acids of the NADPH binding pocket. Analysis of enzyme activity revealed that 17 β -HSD1 was irreversibly inhibited by the sulfhydryl modifying agents N-ethylmaleimide (NEM) and dithiocarbamates. Preincubation with increasing concentrations of NADPH protected 17 β -HSD1 from inhibition by these chemicals. Cys(10)Ser mutant 17 β -HSD1 was partially protected from inhibition by NEM and dithiocarbamates, emphasizing the importance of Cys(10) in the cofactor binding region. Substitution of Cys(10) with serine resulted in a decreased protein half-life, without significantly altering kinetic properties. Despite the fact that Cys(10) on 17 β -HSD1 seems to have limited potential as a target for new enzyme inhibitors, the present study provides new insight into the structure-function relationships of this enzyme

When Neuroscience Meets Pharmacology: A Neuropharmacology Literature Analysis

Background: Considering the enormous progress in the field of neuropharmacology and its global importance, as well as the lack of bibliometric studies examining this field as a whole, it is a high time to assess the prevailing topics and citation performances of its research works.Methods: Web of Science (WoS) was searched to identify relevant neuropharmacology articles, which were analyzed with reference to (1) publication year, (2) journal title, (3) total citation count, (4) authorship, (5) WoS category, and (6) manuscript type. The identified manuscripts were analyzed with VOSviewer for further bibliometric parameters, such as citation analysis of institutions, countries/regions, and journals, and to visualize the citation patterns of the terms appearing in the titles and abstracts.Results: The literature search resulted in 43,354 manuscripts. Nearly 98% of them were published since the 1990s. The majority of the manuscripts were original articles (n = 31,360) and reviews (n = 11,266). The top five WoS categories associated with the analyzed manuscripts were Pharmacology/Pharmacy (n = 14,892, 34.3%), Neurosciences (n = 11,747, 27.1%), Clinical Neurology (n = 4,981, 11.5%), Psychiatry (n = 4,464, 10.3%), and Biochemistry/Molecular Biology (n = 4,337, 10.0%). Seven of the top ten most prolific institutions were located in the USA, and one each in Canada, Italy, and the UK, respectively. Manuscripts mentioning certain molecules or pharmaceuticals had high citations per manuscript, such as those reporting about anandamide, tetrahydrocannabinol (THC), L-glutamate, clozapine, and curcumin. These terms with at least 50 citations per manuscript were mostly related to cannabis and anti-psychotic drugs, with some dealing with anti-epilepsy effects and Alzheimer's disease.Conclusion: We have identified and analyzed all neuropharmacology articles published since the 1990s. Importantly, the area of neuropharmacology research has been growing steadily due to the global trend in population aging and associated with this continuously increasing number of patients with neuropsychiatric disorders worldwide. It is hoped that identification of new pharmaceutically useful molecules or new clinical applications will continue in the future, in order to improve clinical outcomes and to further strengthen the field of neuropharmacology, a research area cross-linking basic and clinical sciences

Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis

Background: Monoamine oxidases (MAOs) were discovered nearly a century ago. This article aims to analyze the research literature landscape associated with MAOs as privileged class of neuronal enzymes (neuroenzymes) with key functions in the processes of neurodegeneration, serving as important biological targets in neuroscience. With the accumulating publications on this topic, we aimed to evaluate the publication and citation performance of the contributors, reveal the popular research themes, and identify its historical roots.Methods: The electronic database of Web of Science (WoS) Core Collection was searched to identify publications related to MAOs, which were analyzed according to their publication year, authorship, institutions, countries/regions, journal title, WoS category, total citation count, and publication type. VOSviewer was utilized to visualize the citation patterns of the words appearing in the titles and abstracts, and author keywords. CRExplorer was utilized to identify seminal references cited by the MAO publications.Results: The literature analysis was based on 19,854 publications. Most of them were original articles (n = 15,148, 76.3%) and reviews (n = 2,039, 10.3%). The top five WoS categories of the analyzed MAO publications were Pharmacology/Pharmacy (n = 4,664, 23.5%), Neurosciences (n = 4,416, 22.2%), Psychiatry (n = 2,906, 14.6%), Biochemistry/Molecular Biology (n = 2,691, 13.6%), and Clinical Neurology (n = 1,754, 8.8%). The top 10 institutions are scattered in the United States, UK, France, Sweden, Canada, Israel, and Russia, while the top 10 countries/regions with the most intensive research on the field of MAOs are the United States, followed by European and Asian countries. More highly cited publications generally involved neurotransmitters, such as dopamine (DA), serotonin, and norepinephrine (NE), as well as the MAO-A inhibitors moclobemide and clorgyline, and the irreversible MAO-B inhibitors selegiline and rasagiline.Conclusion: Through decades of research, the literature has accumulated many publications investigating the therapeutic effects of MAO inhibitors (MAOIs) on various neurological conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression. We envision that MAO literature will continue to grow steadily, with more new therapeutic candidates being tested for better management of neurological conditions, in particular, with the development of multi-target acting drugs against neurodegenerative diseases

Ethnopharmacological Approaches for Therapy of Jaundice: Part I

Jaundice is a very common symptom especially in the developing countries. It is associated with several hepatic diseases which are still major causes of death. There are many different approaches to jaundice treatment and the growing number of ethnomedicinal studies shows the plant pharmacology as very promising direction. Many medicinal plants are used for the treatment of jaundice, however a comprehensive review on this subject has not been published. The use of medicinal plants in drug discovery is highly emphasized (based on their traditional and safe uses in different folk medicine systems from ancient times). Many sophisticated analytical techniques are emerging in the pharmaceutical field to validate and discover new biologically active chemical entities derived from plants. Here, we aim to classify and categorize medicinal plants relevant for the treatment of jaundice according to their origin, geographical location, and usage. Our search included various databases like Pubmed, ScienceDirect, Google Scholar. Keywords and phrases used for these searches included: “jaundice,” “hyperbilirubinemia,” “serum glutamate,” “bilirubin,” “Ayurveda.” The first part of the review focuses on the variety of medicinal plant used for the treatment of jaundice (a total of 207 medicinal plants). In the second part, possible mechanisms of action of biologically active secondary metabolites of plants from five families for jaundice treatment are discussed

Immune Status of Individuals with Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Individuals with spinal cord injury (SCI) have higher infection rates compared to those without SCI. In this review, the immune status difference between individuals with and without traumatic SCI is investigated by examining their peripheral immune cells and markers. PubMed, Cochrane, EMBASE, and Ovid MEDLINE were searched without language or date restrictions. Studies reporting peripheral immune markers' concentration and changes in functional capabilities of immune cells that compared individuals with and without SCI were included. Studies with participants with active infection, immune disease, and central nervous system (CNS) immune markers were excluded. The review followed the PRISMA guidelines. Effect estimates were measured by Weighted Mean Difference (WMD) using a random-effects model. Study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. Fifty-four studies (1813 with SCI and 1378 without SCI) contributed to the meta-analysis. Leukocytes (n = 23, WMD 0.78, 95% CI 0.17; 1.38, I2 83%), neutrophils (n = 11, WMD 0.76, 95% CI 0.09; 1.42, I2 89%), C-reactive protein (CRP) (n = 12, WMD 2.25, 95% CI 1.14; 3.56, I2 95%), and IL6 (n = 13, WMD 2.33, 95% CI 1.20; 3.49, I2 97%) were higher in individuals with SCI vs. without SCI. Clinical factors (phase of injury, completeness of injury, sympathetic innervation impairment, age, sex) and study-related factors (sample size, study design, and serum vs. plasma) partially explained heterogeneity. Immune cells exhibited lower functional capability in individuals with SCI vs. those without SCI. Most studies (75.6%) had a moderate risk of bias. The immune status of individuals with SCI differs from those without SCI and is clinically influenced by the phase of injury, completeness of injury, sympathetic innervation impairment, age, and sex. These results provide information that is vital for monitoring and management strategies to effectively improve the immune status of individuals with SCI

An updated overview on nanonutraceuticals: focus on nanoprebiotics and nanoprobiotics

Over the last few years, the application of nanotechnology to nutraceuticals has been rapidly growing due to its ability to enhance the bioavailability of the loaded active ingredients, resulting in improved therapeutic/nutraceutical outcomes. The focus of this work is nanoprebiotics and nanoprobiotics, terms which stand for the loading of a set of compounds (e.g., prebiotics, probiotics, and synbiotics) in nanoparticles that work as absorption enhancers in the gastrointestinal tract. In this manuscript, the main features of prebiotics and probiotics are highlighted, together with the discussion of emerging applications of nanotechnologies in their formulation. Current research strategies are also discussed, in particular the promising use of nanofibers for the delivery of probiotics. Synbiotic-based nanoparticles represent an innovative trend within this area of interest. As only few experimental studies on nanoprebiotics and nanoprobiotics are available in the scientific literature, research on this prominent field is needed, covering effectiveness, bioavailability, and safety aspects.The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007. E. B. Souto acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Use of #NutritionFacts to promote evidence-based nutrition information: X (formerly Twitter) hashtag analysis study

Nutrition is a key determinant of health, and the dissemination of reliable nutrition information to consumers is of great importance for public health. Especially with the rise of digital communication technologies and the wide-spread online misinformation, the provision of qualitative science-based information related to diet is of great importance. The NutritionFacts.org has been established as a prominent online source of evidence-based nutrition information. In this work we aimed to investigate the use of the associated hashtag #NutritionFacts on X (formerly Twitter) over a 5 years period, from 10th of April 2018 to 10th of April 2023. The conducted analysis with the use of Symplur Signals revealed that 18,998 tweets mentioning #NutritionFacts were posted by 6,136 X users, generating a total of 50,348,223 impressions (views). Both institutional and individual accounts were broadly participating in the dissemination of #NutritionFacts tweets, and the user location profiling indicated wide international engagement with the hashtag. This work indicates that #NutritionFacts has been established as an important hashtag utilized on X for the dissemination of evidence-based information related to nutrition