331 research outputs found
Respiratory Trajectories and Correlation with Serum Biochemical Indices in Spinal and Bulbar Muscular Atrophy
No full textfirst_pagesettingsOrder Article Reprints
Open AccessArticle
Respiratory Trajectories and Correlation with Serum Biochemical Indices in Spinal and Bulbar Muscular Atrophy
by Federica Ginanneschi *,Caterina Bigliazzi,Flora Anna Cimmino,Stefania Casali,Pietro Pelliccioni,Emanuele Emmanuello,Elena BargagliORCID andNicola De Stefano
Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy
*
Author to whom correspondence should be addressed.
Brain Sci. 2024, 14(11), 1057; https://doi.org/10.3390/brainsci14111057
Submission received: 4 September 2024 / Revised: 22 October 2024 / Accepted: 24 October 2024 / Published: 25 October 2024
(This article belongs to the Section Neuromuscular and Movement Disorders)
Downloadkeyboard_arrow_down Browse Figures Versions Notes
Abstract
Background/Objectives: The primary life-threatening complication in spinal–bulbar muscular atrophy (SBMA) is ventilatory failure. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years. Methods: We collected data from 9 genetically confirmed SBMA patients. Spirometric measurements [maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)], serum biochemical indices and SBMA functional rating scale (SBMAFRS) were collected every 6 months for 11 years. An average time curve was utilized to assess the changes in both pulmonary tests and serum biochemical indices of the patients. One-way repeated-measures ANOVA was applied to assess statistical differences. The Spearman’s rank correlation coefficient was utilized to evaluate the correlations between the respiratory function tests and serum biochemical and clinical indices. Results: A progressive decrease was observed in the respiratory function tests; the slope of the linear regression was significantly non-zero (p < 0.0001) for all three time curves. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with FVC (r = 0.27), MIP (r = 0.53) and MEP (r = 0.51). MIP and MEP correlated with creatine phosphokinase (r = 0.3, r = 0.25, respectively) and MIP with creatinine levels (r = 0.31). Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in SBMA patients. The decline appears to be related to clinical deterioration and muscle denervation. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC
Tre ritratti collerici: Giambattista Vico, Gherardo degli Angioli, Angela Cimmino
No full textRilettura di tre ritratti ‘umorali’ di Vico: il primo dedicato a se stesso e posto all’inizio dell’autobiografia; il secondo contenuto in un’epistola indirizzata al poeta Gherardo degli Angioli, il terzo rappresentato da un’orazione funebre rivolta ad Angela Cimmino marchesa della Petrella. I testi risalgono tutti agli anni Venti del Settecento e costituiscono nel loro insieme una riflessione filosofica sui sentimenti della collera e della malinconia
A classification of total order specifications and its application to fixed sequencer-based implementations
No full textDuring the last two decades the design and development of total order (TO) communications has been one of the main research topics in dependable distributed computing. The huge amount of research work has produced several TO specifications and a wide variety of TO implementations with different guarantees whose differences are often left hidden or unclear. This paper presents a systematic classification of six distinct TO specifications based on a well-defined formal framework. The classification allows us (i) to define in a formal way the differences among the behaviors of faulty and correct processes admitted by each specification, and (ii) to easily match TO implementations with respect to their enforced specification. The classification is applied to study the properties of eight variations of TO implementations based on a fixed sequencer given in a well-known context, namely primary component group communication systems. (c) 2005 Elsevier Inc. All rights reserved
Absolute configuration of fungal metabolites phyllostin and scytolide by ORD, ECD, and VCD computational analysis
No full textDue to recent advance in theoretical predictions of chiroptical properties, and the progress in computation and instrumental technology, all three methods of Optical Rotatory Dispersion (ORD), Electronic (ECD) and Vibrational Circular Dichroism (VCD) can provide nowadays very reliable approaches for assignment of the molecular absolute configuration (AC) in solution. However, in some instances, to avoid any ambiguity in configurational assignment, the use of more than one single method is justified.
In this work we present a determination of AC of two bioactive fungal metabolites, phyllostin[1] and scytolide,[2] by combined employment of theoretical/experimental analysis of their ORD, ECD, and VCD properties. We provide evidences justifying the necessity of multiple methods for safest possible AC assignment of both compounds.
References
[1] A. Evidente, A. Cimmino, A. Andolfi, M. Vurro, M.C. Zonno, A. Motta, J. Agric. Food Chem. 56 884 (2008)
[2] W.A. Ayer, Y. Fukazawa, H. Orszanska, Nat. Prod. Lett. 2 77 (1993
Polydatin-mediated shift in redox balance and its anti-cancer effects on osteosarcoma cells in vitro
No full textOsteosarcoma (OS), the most common bone cancer in children and young adults, remains a significant therapeutic challenge due to high rates of metastasis and drug resistance. Polydatin (PD), a natural glucoside derivative of resveratrol, has shown promising anti-cancer activity, particularly through its regulation of oxidative stress, cell cycle arrest, and apoptosis induction. This study explores for the first time the redox-dependent anti-cancer effects of PD on SAOS-2 and U2OS cells. It investigates ROS modulation, glutathione (GSH) depletion, and ferroptosis markers, including total iron and intracellular malondialdehyde (MDA), using assay kits. The involvement of oxidative stress regulators such as SIRT1 and Nrf2 was also assessed through Western blot and real-time PCR analyses. Additionally, cell-based biochemical assays were employed to evaluate the efficacy of PD under tumor-like conditions of hypoxia and serum starvation.The study further examines PD’s potential as an adjuvant therapy for OS by assessing its synergistic effects on OS cell viability and proliferation when combined with ROS-inducing chemotherapeutic agents, doxorubicin (DOX) and cisplatin (CIS). My findings provide the first evidence that PD-induced redox imbalance is a critical mechanism underlying its anti-cancer
activity in SAOS-2 and U2OS cells. By elevating intracellular ROS levels, depleting GSH and increasing intracellular levels of both total iron and MDA (markers of ferroptosis), PD sensitizes OS cells to oxidative stress-related cell death, making them more vulnerable to survival challenges, particularly under hypoxic conditions and drug treatments. Importantly, PD exhibited minimal toxicity to normal osteoblast cells (hFOB 1.19), suggesting a favorable therapeutic window. These
results indicate that PD warrants further investigation to elucidate the precise molecular driving its pro-oxidant effects in OS
Total order communications: a practical analysis
No full textTotal Order (TO) broadcast is a widely used communication abstraction that has been deeply investigated during the last decade. As such, the amount of relevant works may leave practitioners wondering how to select the TO implementation that best fits the requirements of their applications. Different implementations are indeed available, each providing distinct safety guarantees and performance. These aspects must be considered together in order to build a correct and sufficiently performing application. To this end, this paper analyzes six TO implementations embedded in three freely-distributed group communication systems, namely Ensemble, Spread and JavaGroups. Implementations are first classified according to the enforced specifications, which is given using a framework for specification tailored to total order communications. Then, implementations are compared under the performance viewpoint in a simple yet meaningful deployment scenario. In our opinion, this structured information should assist practitioners (i) in deeply understanding the ways in which implementations may differ (specifications, performance) and (ii) in quickly relating a set of total order algorithms to their specifications, implementations and performance
Computational ECD Spectrum Simulation of the Phytotoxin Scytalone: Importance of Solvent Effects on Conformer Populations
No full textA time-dependent Density Functional Theory (TDDFT) computational simulation of the electronic circular dichroism (ECD) spectrum of the phytotoxin scytalone (1), produced by different plant pathogenic fungi and involved in melanin production, was undertaken with the aim to establish a nonempirical correlation between the spectrum and the absolute configuration of this compound. In fact, very low optical rotation data of 1 do not afford a reliable absolute configuration assignment while, on the contrary, the use of ECD can provide a useful tool for its stereochemical description. This structurally simple molecule displayed a considerable molecular flexibility, which made it mandatory to obtain an accurate conformers distribution to get a good reproduction of the experimental ECD spectrum. Only the application of an implicit integral equation formalism Polarizable Continuum Model (IEF-PCM) solvation model in the calculations allowed us to properly describe the conformer populations and finally obtain a more than satisfactory spectral simulatio
Amaryllidaceae alkaloids: Absolute configuration and biological activity
No full textPlants belonging to the Amaryllidaceae family are well known for their ornamental and medicinal use. Plant members of this group are distributed through both tropical and subtropical regions of the world and are dominant in Andean South America, the Mediterranean basin, and southern Africa. Amaryllidaceae plants have been demonstrated to be a good source of alkaloids with a large spectrum of biological activities, the latter being strictly related to the absolute stereochemistry of the alkaloid scaffold. Among them, great importance for practical applications in medicine has galanthamine, which has already spawned an Alzheimer's prescription drug as a potent and selective inhibitor of the enzyme acetylcholinesterase. Furthermore, lycorine as well as its related isocarbostyryl analogs narciclasine and pancratistatine have shown a strong anticancer activity in vitro against different solid tumors with malignant prognosis. This review addresses the assignment of the absolute configuration of several Amaryllidaceae alkaloids and its relationship with their biological activities
Application of Mosher's method for absolute configuration assignment to bioactive plants and fungi metabolites
No full textThe review deals with the application of the NMR advanced Mosher's method for the assignment of the absolute configuration to plant and fungal metabolites belonging to different classes of natural compounds. The structural and stereochemical characterization of these naturally occurring metabolites, as well as their biological properties as possible drugs or agrochemicals is reviewed. The importance of the absolute and relative stereochemistry on their biological properties is also highlighted. Successes and failures of application of the advanced Mosher's method are reported
Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization
No full textFungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites
- …
