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Abstract Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2–4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC50 values ranging from 14.5 to 24.6 μM, with compound (1) being the most potent as compared to the positive control thiourea (IC50 = 21.6 μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC50 = 17.9 μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2–4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors. Graphical Abstract

Stem cell therapy represents a transformative frontier in medical science, offering promising avenues for revolutionizing cancer treatment and advancing our understanding of neurobiology. This review explores innovative approaches in stem cell therapy that have the potential to reshape clinical practices and therapeutic outcomes in cancer and neurodegenerative diseases. In this dynamic and intriguing realm of cancer research, recent years witnessed a surge in attention toward understanding the intricate role of mesenchymal stem cells (MSCs). These cells, capable of either suppressing or promoting tumors across diverse experimental models, have been a focal point in the exploration of exosome-based therapies. Exosomes released by MSCs have played a pivotal role, in unraveling the nuances of paracrine signaling and its profound impact on cancer development. Recent studies have revealed the complex nature of MSC-derived exosomes, showcasing both protumor and antitumor effects. Despite their multifaceted involvement in tumor growth, these exosomes show significant promise in influencing both tumor development and chemosensitivity, acting as a pivotal factor that increases stem cells' potential for medicinal use. Endogenous MSCs, primarily originating from the bone marrow, exhibited a unique migratory response to damaged tissue sites. The genetic modification of stem cells, including MSCs, opened avenues for the precise delivery of therapeutic payloads in the milieu around the tumor (TME). Stem cell therapy offers groundbreaking potential for treating neurodegenerative and autoimmune disorders by regenerating damaged tissues and modulating immune responses. This approach aims to restore lost function and promote healing through targeted cellular interventions. In this review, we explored the molecular complexities of cancer and the potential for breakthroughs in personalized and targeted therapies. This analysis offers hope for transformative advancements in both cancer treatment and neurodegenerative disorders, highlighting the promise of precision medicine in addressing these challenging conditions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cannabis use disorder (CUD) is associated with adverse mental health effects, as well as social and cognitive impairment. Given prevalence rates of CUD are increasing, there is considerable efforts, and need, to identify prognostic markers which may aid in minimising any harm associated with this condition. Previous neuroimaging studies have revealed changes in white matter (WM) organization in people with CUD, though, the findings are mixed. In this study, we applied MRI-based analysis techniques that offer complimentary mechanistic insights, i.e., a connectome approach and fixel-based analysis (FBA) to investigate properties of individual WM fibre populations and their microstructure across the entire brain, providing a highly sensitive approach to detect subtle changes and overcome limitations of previous diffusion models. We compared 56 individuals with CUD (median age 25 years) to a sample of 38 healthy individuals (median age 31.5 years). Compared to controls, those with CUD had significantly increased structural connectivity strength (FDR corrected) across 9 edges between the right parietal cortex and several cortical and subcortical regions, including left orbitofrontal, left temporal pole, and left hippocampus and putamen. Utilizing FBA, WM density was significantly higher in those with CUD (FWE-corrected) across the splenium of the corpus callosum, and lower in the bilateral cingulum and right cerebellum. We observed significant correlation between cannabis use over the past month and connectivity strength of the frontoparietal edge, and between age of regular use and WM density of the bilateral cingulum and right cerebellum. Our findings enhance the understanding of WM architecture alterations associated with CUD., (© 2024. The Author(s).)

Background and Purpose: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls., Materials and Methods: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses., Results: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity., Conclusions: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders., (© 2023 by American Journal of Neuroradiology.)

Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long-Evans rats ( n  = 14) compared with sham animals ( n  = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats ( P  < 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4-6-week remission following a first episode of psychosis., Method: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts., Results: Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naïve. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P < .0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P < .0001), demonstrating reliability., Conclusions: Using items from common and validated clinical scales, our model significantly predicted early remission in patients with first-episode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians' assessment should be undertaken to evaluate the possible utility as a routine clinical tool., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

23 Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T 2 ∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23 Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23 Na T 2 ∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 ​T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1 H/ 23 Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1 H receive coil. 23 Na T 2 ∗ relaxation parameters [mean T 2 ∗ (T 2 ∗ mean ) and fast relaxation fraction (T 2 ∗ ff )] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T 2 ∗ mean and T 2 ∗ ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T 2 ∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue., Competing Interests: Declaration of competing interest The authors report no conflicts of interest relating to this work., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)