Theonella: A Treasure Trove of Structurally Unique and Biologically Active Sterols

: The marine environment is considered a vast source in the discovery of structurally unique bioactive secondary metabolites. Among marine invertebrates, the sponge Theonella spp. represents an arsenal of novel compounds ranging from peptides, alkaloids, terpenes, macrolides, and sterols. In this review, we summarize the recent reports on sterols isolated from this amazing sponge, describing their structural features and peculiar biological activities. We also discuss the total syntheses of solomonsterols A and B and the medicinal chemistry modifications on theonellasterol and conicasterol, focusing on the effect of chemical transformations on the biological activity of this class of metabolites. The promising compounds identified from Theonella spp. possess pronounced biological activity on nuclear receptors or cytotoxicity and result in promising candidates for extended preclinical evaluations. The identification of naturally occurring and semisynthetic marine bioactive sterols reaffirms the utility of examining natural product libraries for the discovery of new therapeutical approach to human diseases

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis.

Abstract Objective To explore anti-inflammatory activities of organic extract and its semi-purified fractions (ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results The fraction F–EtOH showed an important anti-inflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases

Swinholide J, a Potent Cytotoxin from the Marine Sponge Theonella swinhoei

In our ongoing search for new pharmacologically active leads from Solomon organisms, we have examined the sponge Theonella swinhoei. Herein we report the isolation and structure elucidation of swinholide A (1) and one new macrolide, swinholide J (2). Swinholide J is an unprecedented asymmetric 44-membered dilactone with an epoxide functionality in half of the molecule. The structural determination was based on extensive interpretation of high-field NMR spectra and HRESIMS data. Swinholide J displayed potent in vitro cytotoxicity against KB cells (human nasopharynx cancer) with an IC50 value of 6 nM

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of C-13 chemical shifts

In this paper the stereostructural investigation of two new oxygenated polyketides, plakilactones G and H, isolated from the marine sponge Plakinastrella mamillaris collected at Fiji Islands, is reported. The stereostructural studies began on plakilactone H by applying an integrated approach of the NOE-based protocol and quantum mechanical calculations of (13)C chemical shifts. In particular, plakilactone H was used as a template to extend the application of NMR-derived interproton distances to a highly flexible molecular system with simultaneous assignment of four non-contiguous stereocenters. Chemical derivatization and quantum mechanical calculations of (13)C on plakilactone G along with a plausible biogenetic interconversion between plakilactone G and plakilactone H allowed us to determine the absolute configuration in this two new oxygenated polyketides

Chronic pain and spinal cord stimulation.

Chronic pain can have a devastating impact and lead to patient isolation. Many people with chronic pain are predisposed to anxiety-depressant symptoms, due to a lower quality life. The aim of the study is to demonstrate how neuromodulation methods, can encourage the reduction of chronic pain and an improvement in the quality of life, therefore advancing the restoration of psychological well-being.We involved 50 patients with a diagnosis of pain that not respond to traditional pharmacological therapies. Interventions: All subject had depression and anxiety symptoms and a low-quality life. We used the spinal cord stimulation treatment and a psychological evaluation for assessment of depression-anxiety symptomatology and the level of quality life.We observed a significant difference in physical functioning, role limitations due to physical health, general health perceptions, vitality, social functioning, role limitations due to emotional problems and mental health.Our study affirms that the perception of chronic pain has a great impact on the perception of psychological well-being, quality of life, and the performance of normal daily social and professional activities

Tracing kinematic (mis)alignments in CALIFA merging galaxies: Stellar and ionized gas kinematic orientations at every merger stage

We present spatially resolved stellar and/or ionized gas kinematic properties for a sample of 103 interacting galaxies, tracing all merger stages: close companions, pairs with morphological signatures of interaction, and coalesced merger remnants. We compare our sample with 80 non-interacting galaxies. We measure for the stellar and the ionized gas components the major (projected) kinematic position angles (PA$_{\mathrm{kin}}$, approaching and receding) directly from the velocity fields with no assumptions on the internal motions. This method allow us to derive the deviations of the kinematic PAs from a straight line ($\delta$PA$_{\mathrm{kin}}$). Around half of the interacting objects show morpho-kinematic PA misalignments that cannot be found in the control sample. Those misalignments are present mostly in galaxies with morphological signatures of interaction. Alignment between the kinematic sides for both samples is similar, with most of the galaxies displaying small misalignments. Radial deviations of the kinematic PA from a straight line in the stellar component measured by $\delta$PA$_{\mathrm{kin}}$ are large for both samples. However, for a large fraction of interacting galaxies the ionized gas $\delta$PA$_{\mathrm{kin}}$ is larger than typical values derived from isolated galaxies (48%), making this parameter a good indicator to trace the impact of interaction and mergers in the internal motions of galaxies. By comparing the stellar and ionized gas kinematic PA, we find that 42% (28/66) of the interacting galaxies have misalignments larger than 16 degrees, compared to 10% from the control sample. Our results show the impact of interactions in the internal structure of galaxies as well as the wide variety of their velocity distributions. This study also provides a local Universe benchmark for kinematic studies in merging galaxies at high redshift.Comment: 24 pages,11 Figures, Accepted for publication in Astronomy & Astrophysics. The entire set of stellar and ionized gas velocity fields of the interacting/merging sample will be available in the electronic version of the journa

Bioactive cembrane derivatives from the Indian Ocean soft coral, Sinularia kavarattiensis

Marine organisms and their metabolites represent a unique source of potential pharmaceutical substances. In this study, we examined marine-derived substances for their bioactive properties in a cell-based Chikungunya virus (CHIKV) replicon model and for in vitro anti-inflammatory activity. In the screening of a marine sample library, crude extracts from the Indian soft coral, Sinularia kavarattiensis, showed promising activity against the CHIKV replicon. Bioassay-guided chemical fractionation of S. kavarattiensis resulted in the isolation of six known norcembranoids (1–6) and one new compound, named kavaranolide (7). The structures were elucidated on the basis of NMR and MS spectroscopic data. Compounds 1–3 and 5–7 were evaluated for their replicon-inhibiting potential in the CHIKV model by using a luminescence-based detection technique and live cell imaging. Compounds 1 and 2 showed moderate inhibition of the CHIKV replicon, but imaging studies also revealed cytotoxic properties. Moreover, the effects of the isolated compounds on primary microglial cells, an experimental model for neuroinflammation, were evaluated. Compound 2 was shown to modulate the immune response in microglial cells and to possess potential anti-inflammatory properties by dose-dependently reducing the release of pro- and anti-inflammatory cytokines.Peer reviewe

The Mice at play in the CALIFA survey: A case study of a gas-rich major merger between first passage and coalescence

We present optical integral field spectroscopy (IFS) observations of the Mice, a major merger between two massive (>10^11Msol) gas-rich spirals NGC4676A and B, observed between first passage and final coalescence. The spectra provide stellar and gas kinematics, ionised gas properties and stellar population diagnostics, over the full optical extent of both galaxies. The Mice provide a perfect case study highlighting the importance of IFS data for improving our understanding of local galaxies. The impact of first passage on the kinematics of the stars and gas has been significant, with strong bars likely induced in both galaxies. The barred spiral NGC4676B exhibits a strong twist in both its stellar and ionised gas disk. On the other hand, the impact of the merger on the stellar populations has been minimal thus far: star formation induced by the recent close passage has not contributed significantly to the global star formation rate or stellar mass of the galaxies. Both galaxies show bicones of high ionisation gas extending along their minor axes. In NGC4676A the high gas velocity dispersion and Seyfert-like line ratios at large scaleheight indicate a powerful outflow. Fast shocks extend to ~6.6kpc above the disk plane. The measured ram pressure and mass outflow rate (~8-20Msol/yr) are similar to superwinds from local ULIRGs, although NGC4676A has only a moderate infrared luminosity of 3x10^10Lsol. Energy beyond that provided by the mechanical energy of the starburst appears to be required to drive the outflow. We compare the observations to mock kinematic and stellar population maps from a merger simulation. The models show little enhancement in star formation during and following first passage, in agreement with the observations. We highlight areas where IFS data could help further constrain the models.Comment: 23 pages, 13 figures, accepted to A&A. A version with a complete set of high resolution figures is available here: http://www-star.st-and.ac.uk/~vw8/resources/mice_v8_astroph.pd

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures