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Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs.

Medical educators strive to improve their curricula to enhance the student learning experience. The use of high-fidelity simulation within basic and clinical medical science subjects has been one of these initiatives. However, there is paucity of evidence on using simulation for teaching pharmacology, especially in the Middle East and North Africa region, and the effectiveness of this teaching modality, relative to more traditional ones, have not been sufficiently investigated. Accordingly, this study compares the effects of high-fidelity simulation, which is designed in alignment with adult and experiential learning theories, and traditional case-based tutorial sessions on the performance and perception of undergraduate Year 2 medical students in pharmacology in Dubai, United Arab Emirates. This study employed a convergent mixed methods approach. Forty-nine medical students were randomly assigned to one of two groups during the 16-week pharmacology course. Each group underwent one session delivered via high-fidelity simulation and another via a case-based tutorial. A short multiple-choice question quiz was administered twice (immediately upon completion of the respective sessions and 5 weeks afterwards) to assess knowledge retention. Furthermore, to explore the students' perceptions regarding the two modes of learning delivery (independently and in relation to each other), an evaluation survey was administered following the delivery of each session. Thereafter, the iterative joint display analysis was used to develop a holistic understanding of the effect of high-fidelity simulation in comparison to traditional case-based tutorial sessions on pharmacology learning in the context of the study. There was no statistically significant difference in students' knowledge retention between high-fidelity simulation and case-based tutorial sessions. Yet, students expressed a greater preference for high-fidelity simulation, describing the corresponding sessions as more varied, better at reinforcing learning, and closer to reality. As such, the meta-inferences led to expansion of the overall understanding around students' satisfaction, to both confirmation and expansion of the systemic viewpoint around students' preferences, and lastly to refinement in relation to the perspective around retained knowledge. High-fidelity simulation was found to be as effective as case-based tutorial sessions in terms of students' retention of knowledge. Nonetheless, students demonstrated a greater preference for high-fidelity simulation. The study advocates caution in adapting high-fidelity simulation, where careful appraisal can lend itself to identifying contexts where it is most effective.

Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of data regarding ICI-associated scleroderma which can carry significant morbidity and limit the ability to continue effective ICI therapy. Our review aimed to analyze the current literature on ICI-associated systemic scleroderma (ICI-SSc) and key scleroderma mimics. Cases of ICI-SSc had notable differences from primary SSc, such as fewer vascular features and less seropositivity (such as scleroderma-specific antibodies and antinuclear antibodies). We found that patients with a diagnosis of SSc prior to the start of ICI can also experience flares of pre-existing disease after ICI treatment used for their cancer. Regarding scleroderma mimics, several cases of ICI-eosinophilic fasciitis have also been described with variable clinical presentations and courses. We found no cases of scleroderma mimics: ICI-scleromyxedema or ICI-scleroedema. There is a critical need for multi-institutional efforts to collaborate on developing a patient database and conducting robust, prospective research on ICI-scleroderma. This will ultimately facilitate more effective clinical evaluations and management for ICI-scleroderma.

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010–2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions.

Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The search for effective, new antineoplastic drugs with fewer side effects for the treatment of CRC continues, with marine-derived compounds emerging as promising candidates. Objectives: This study investigates the anticancer potential of Frondanol, a nutraceutical derived from the Atlantic Sea cucumber Cucumaria frondosa, known for its potent anti-inflammatory properties. Methods: Two human CRC cell lines, Caco-2 and HT-29, were used to test the effects of Frondanol using various in vitro approaches. Results: Frondanol significantly inhibited cell viability in a dose- and time-dependent manner. At a 1:10,000 dilution, viability decreased to around 30% in Caco-2 and 20% in HT-29 after 24 h, dropping to nearly 5% at 48 h. Furthermore, a clonogenic assay showed around 50% reduction in colony formation in both cell lines. Flow cytometry-based Annexin V staining revealed that Frondanol increased early apoptosis to ~5.2% in Caco-2 and ~9.4% in HT-29 cells, while cell cycle analysis showed accumulation of the sub G0 (apoptotic) phase increasing from 1.5% to 14.7% (Caco-2) and from 1.9% to 23.8% (HT-29). At the molecular level, Frondanol treatment significantly decreased anti-apoptotic protein B-cell lymphoma (Bcl)-2 expression while increasing the expression of the proapoptotic protein Bcl-2-associated X-protein. Additionally, Frondanol markedly induced cytochrome c release from the mitochondria and activated caspase-9, caspase-7, and caspase-3 after treatment, alongside cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase. Frondanol inhibited 5-lipoxygenase activity, further contributing to its anticancer effects. Conclusions: In conclusion, Frondanol inhibits CRC cell proliferation and induces apoptosis through the mitochondrial pathway in vitro, suggesting that it is a potential nutraceutical for the prevention of human colorectal cancer or a valuable source of anticancer compounds.

Frondanol, a non-polar lipid extract derived from the edible sea cucumber Cucumaria frondosa, has shown promising anti-inflammatory properties. This study investigated its molecular mechanisms in modulating inflammation using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Frondanol was found to be non-cytotoxic at the tested dilutions (1:80,000 to 1:10,000). Co-treatment with LPS and Frondanol significantly reduced the production of inflammatory mediators. Nitric oxide (NO) levels were decreased by up to 30% (p < 0.05), while iNOS protein and mRNA expression were reduced by approximately 45% (p < 0.05) and 80% (p < 0.0001), respectively, at a 1:10 K dilution. Prostaglandin E (PGE ) levels were suppressed by nearly 40% (p < 0.0001), accompanied by a 60% reduction in COX-2 protein (p < 0.01) and a 70% decrease in COX-2 mRNA expression (p < 0.05). The pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin (IL)-6 were also significantly attenuated by Frondanol treatment. Mechanistically, Frondanol inhibited LPS-induced NF-κB activation by reducing IκBα phosphorylation and preventing nuclear translocation of NF-κB p65. Furthermore, Frondanol significantly downregulated the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38. These results suggest that Frondanol exerts its anti-inflammatory effects through suppression of both NF-κB and MAPK signalling pathways, leading to reduced production of inflammatory mediators and cytokines. Given its efficacy and lack of cytotoxicity, Frondanol may hold strong potential as a nutraceutical agent for the prevention and management of chronic inflammatory diseases.

Preeclampsia is 1 of the 3 leading causes of maternal mortality worldwide. Unfortunately, its exact pathogenesis is still unclear. Published metabolomic and gene expression analyses point to coenzyme A (CoA) restriction in the placenta as a factor underpinning the observed complications of preeclampsia, but this hypothesis has never been tested. This pilot study aims to discover evidence supporting the CoA-restriction hypothesis through 2 avenues. The first of these involves developing a procedure for the quantitative determination of metabolites to discover if harmful metabolites are elevated in patients with preeclampsia, while the second seeks to emulate the onset of CoA restriction in cultured cells. This manuscript provides a rationale and a protocol for a clinical study and laboratory experiments to test the hypothesis. The methods have 3 key aspects. Phase 1 comprises optimization of assays of 5 key metabolites arising from CoA restriction, namely L-leucine, ketoisovalerate, ketodeoxycholate, oleic acid, and sphingosine-1-phosphate. Phase 2 comprises recruitment of patients to obtain serum samples to measure the metabolites, and phase 3 comprises culturing and treating trophoblast cells to induce CoA restriction and test the effects of the metabolites on the cells. Patients with preeclampsia and healthy controls will be recruited based on World Health Organization criteria for preeclampsia. Exclusion criteria include multiple pregnancies, premature rupture of membranes, and various medical complications. Blood samples will be collected and analyzed using high-performance liquid chromatography/mass spectrometry (HPLC/MS) to quantify key metabolites associated with CoA restriction. For trophoblast cell studies, BeWo cells will be cultured under conditions likely to induce CoA restriction, including hypoxia and human chorionic gonadotropin supplementation, and will also be treated with the key metabolites to determine what effect they might have. Cell viability, apoptosis, energy metabolism, and gene expression (focusing on genes involved in CoA synthesis and metabolism) will be assessed. Statistical analysis will involve 2-tailed t tests or Mann-Whitney U tests to compare metabolite concentrations between patients with preeclampsia and controls. A correlation matrix will be used to explore associations between metabolite levels and patient characteristics. Institutional review board ethics approval has been obtained for this study. Patient recruitment started April 1, 2025. The 5 metabolites have been purchased in synthetic form and used to optimize the HPLC/MS assays in preparation for receiving blood samples. The trophoblast cell-line culture is being optimized. The findings of this study will demonstrate that key metabolite concentrations can be quantified using HPLC/MS and indicate if CoA restriction is associated with preeclampsia. If so, this provides a significant, novel avenue for research into the treatment and prevention of the disease. PRR1-10.2196/66202.

Autism spectrum disorders (ASD) are associated with disruption of large-scale brain network. Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD. Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. We first determined the predominant microstates using established clustering methods. We identified five predominant microstate (labeled as microstate classes A–E) with significant differences in the temporal dynamics of microstate class B between the groups in terms of increased appearance and prolonged duration. Using Markov chains, we found differences in the dynamic syntax between several maps in toddlers and preschoolers with ASD compared to their TD peers. Finally, exploratory analysis of brain–behavioral relationships within the ASD group suggested that the temporal dynamics of some maps were related to conditions comorbid to ASD during early developmental stages.To assess the association between Autism spectrum disorders (ASD) and the potential disruption of large-scale brain networks, Bochet, Sperdin et al investigated spatiotemporal dynamics of whole-brain neuronal networks in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. They found differences in the dynamic syntax between several maps in toddlers and pre-schoolers with ASD compared to their TD peers.