Advancing Open Science

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with evolving pathogenesis. Biological barriers, especially intestinal and blood–brain barriers (BBBs) with their tight junctions (TJ), are gaining attention in recent years as key players in disease initiation and progression. Among natural products targeting these barriers, cinnamon is emerging as a multi-targeted modulator of TJ. This narrative review integrates current evidence about gut and brain barrier dysfunction in lupus pathogenesis and highlights, on the basis of animal studies, the potential of cinnamon as a therapeutic candidate to restore barrier integrity and attenuate immune and neuroinflammation associated with lupus. Experimental evidence from lupus models supports the role of TJ disruption in disease pathogenesis. The alteration of TJ protein distribution in the epithelial barrier is correlated with an increased permeability of the intestinal barrier and changes in the microbiota composition in lupus, with consequent alteration in the gut–liver axis, liver inflammation and oxidative stress. Pre-clinical studies have demonstrated the restorative effect of cinnamon on gut TJ and permeability, microbiota and the gut–liver axis. Moreover, accumulating data suggest BBB disruption in lupus, correlated with neuroinflammation and behavioral disturbances. A murine model demonstrates the protective effect of cinnamon on BBB, especially via TJ localization, with the alleviation of neuropsychiatric alterations. Future perspectives should focus on cinnamon’s effect on the gut–brain axis and translational studies.

Background: Atherosclerosis is a major pathological basis of cardiovascular disease and is influenced by both genetic and environmental factors. Although genome-wide association studies have identified the LAMB2 p.E987K variant as a susceptibility locus for atherosclerosis, its functional role remains unclear. Methods: In this study, a rabbit model carrying the homologous LAMB2 p.E991K mutation was generated using the CRISPR/Cas9-SpG system and subjected to a high-fat diet to induce atherosclerosis. Results: LAMB2 mutant rabbits exhibited increased body weight and significant lipid metabolic abnormalities. Oil Red O staining demonstrated enhanced lipid accumulation and larger atherosclerotic plaques in the aorta. In addition, α-SMA expression was reduced, whereas CD4 and MCP-1 expression was elevated, suggesting vascular smooth muscle cell loss and altered immune responses. Laminin β2 (LAMB2) expression was markedly decreased and accompanied by basement membrane disruption. Furthermore, activation of the NLRP3 inflammasome was observed in mutant rabbits. Conclusions: These findings demonstrate that the LAMB2 p.E991K mutation promotes HFD-induced atherosclerosis by impairing basement membrane integrity, enhancing inflammation, and disrupting lipid metabolism, highlighting LAMB2 as a genetic modifier of atherosclerosis susceptibility.

A previous study identified [¹¹C]M503-1619 as a lead compound for positron emission tomography (PET) radiotracer development. The goal of the current study was to conduct a structure–activity relationship (SAR) study on M503-1619 to improve its in vitro binding affinity for alpha synuclein (aSyn), as well as to identify potential radiotracers that could be labeled with fluorine-18. The results of the SAR study identified strict SARs regarding the introduction of a fluorine into the N-aryl piperazine and benzamide moieties. The most promising compound was the corresponding 2-fluoroethyl analog of M503-1619. This compound was radiolabeled with fluorine-18, followed by in vivo PET imaging studies on non-human primate and in vitro autoradiography study. In vitro autoradiography studies in human postmortem brain sections demonstrated that ¹⁸F-labeled radiotracer has higher binding to synucleinopathies versus control brain tissues. This radiotracer displays the high initial brain uptake and rapid washout that is needed for a PET radiotracer for imaging a protein such as aSyn that has a low target density in the brain. However, the formation of brain penetrant radiolabeled metabolites prevented further evaluation of this compound. Insights from this SAR study are guiding the development of novel aSyn radioligands that avoid formation of the undesirable radiolabeled metabolite.

Background/Objectives: There is increasing interest in and evidence for the role of ultra-processed foods (UPFs) in cardiometabolic risk. We tested the hypothesis that UPF intake score derived from dietary history is associated with measures of insulin secretion and sensitivity in a family setting even when the process of type 2 diabetes is still to ensue. Methods: We used data from our well-characterized San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) study cohort of nondiabetic children (aged 6–17 years). Dietary history was assessed using the Block Food Frequency Questionnaire. Outcomes of interest were 19 clinically useful indexes of insulin secretion/sensitivity based on fasting and oral glucose tolerance test results. Since the SAFARI study employed a family study design, we used polygenic regression models that adjusted for complex interactions between age and sex and accounted for important comorbidities. Results: A total of 53.3% of daily energy intake was contributed by UPF. Of the 19 indexes tested for association with the UPF score, we found a statistically significant association with measures of insulin resistance and beta cell function and with three indexes based on the results of oral glucose tolerance test as follows: Matsuda index (β = −0.0962, p = 0.0262), insulinogenic index at 30 min (β = 0.1779, p = 0.0006) and disposition index at 30 min (β = 0.1538, p = 0.0061). Conclusions: Even in nondiabetic children there was a significant and independent association of UPF intake with insulin secretion and sensitivity. Future studies need to investigate this association in larger, longitudinal settings and in randomized trials controlling potential systematic errors.

The omics sciences represent a revolution for clinical studies, offering integrative approaches to analyzing biological data with unprecedented depth. From the discovery of the double-helix structure of DNA to the CRISPR-Cas9 gene editing tool, passing through the evolution of sequencing platforms and the exponential advance of computing power and in silico tools, omics has progressed in its role of leading innovative solutions for old challenges in health sciences. In this review, we describe different omics, the history of their techniques and technologies, data analysis and up-to-date visualization tools used for clinical data in research and health systems. We also discuss how omics are currently being applied in diagnosis, precision and personalized medicine. For the future, omics vow to underpin the majority of decisions made by health professionals, allowing individualized treatments based on Big Data and personal biological information.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predictive value of circulating HSPs in both solid and hematological cancers. Clinical studies indicate that circulating HSP concentrations are associated with tumor type, disease stage, lymph node involvement, metastatic burden, treatment response, and risk of recurrence. Importantly, membrane-associated and extracellular vesicle-associated forms of HSP70 appear to exhibit greater tumor specificity than freely circulating proteins, highlighting the importance of selecting appropriate analytical approaches for biomarker assessment. Beyond their utility as biomarkers, extracellular HSPs actively participate in tumor biology and anti-tumor immunity. Depending on the cellular and immunological context, they can either support tumor progression or stimulate immune responses through activation of natural killer cells, antigen-presenting cells, and cross-presentation of tumor-derived antigens. These immunomodulatory properties have provided the foundation for the development of HSP-based vaccines and adoptive immunotherapeutic strategies, several of which have demonstrated encouraging results in clinical trials. We further discuss the relationship between extracellular chaperone biology and responses to major anticancer treatments, including radiotherapy, chemotherapy, HSP90-targeted therapies, and immune checkpoint blockade. In conclusion, the available evidence supports circulating extracellular HSPs as promising non-invasive biomarkers and potential pharmacodynamic indicators that may improve patient stratification, treatment monitoring, and prediction of therapeutic efficacy in clinical oncology.

Background: This study aimed to identify the field-based technical and biomechanical variables that best discriminate and predict competitive performance in 11–12-year-old swimmers. Methods: Seventy-two federated swimmers were assessed during a controlled technical evaluation session conducted four weeks prior to the Under-13 (U–13) Regional Championship. Variables measured included 25 m freestyle time and velocity, 25 m kick time and velocity, turn time and velocity using the 5 m in–5 m out criterion, stroke count, stroke length, and swimming efficiency index. Aqua Points were obtained from official championship results held one month after testing. Swimmers were categorized into three performance groups according to Aqua Points classification: low, medium, and high competitive level. A multiple linear regression analysis was performed to identify predictors of competitive performance. Results: Significant differences were observed between competitive levels for 25 m freestyle time and velocity, kick performance, turn time and velocity, and swimming efficiency (p < 0.05), with progressive improvements as Aqua Points increased. Significant differences were also observed for stroke count and stroke length, suggesting that stroke mechanics contributed to performance differentiation within this age group. In the regression analysis, 25 m freestyle velocity and turn velocity emerged as the strongest predictors of competitive performance, while sex was a significant covariate. The final model explained a large proportion of the variance in Aqua Points (R² = 0.846, adjusted R² = 0.832, p < 0.001). Conclusions: Competitive level in 11–12-year-old swimmers is strongly associated with technical proficiency, particularly short-distance swimming speed and turn execution. These findings highlight the importance of technical development during formative stages and provide practical insights for coaching strategies.

Fucus vesiculosus (FV) is a brown macroalga rich in bioactive compounds with significant industrial potential. This study aimed to produce enzyme-assisted water-soluble hydrolysates from FV with optimized antioxidant activity using Box–Behnken experimental designs. Two extraction methods were evaluated: cellulase alone (FVc) and a combination of cellulase and alcalase (FVca). The optimization focused on enzyme concentration, temperature, and incubation time, measuring extraction yield, total phenolic content as determined by the Folin–Ciocalteu assay (non-specific reducing capacity index, FC-derived TPC), total antioxidant capacity (TAC), and oxygen radical absorbance capacity (ORAC). Results demonstrated that the combined dual-enzyme (FVca) treatment was highly efficient, simultaneously maximizing the extraction yield (39.41%) and the overall reducing capacity (TAC of 142.80 µmol TE/g, ORAC of 477.64 µmol TE/g, and a FC-derived TPC of 252.57 mg GAE/g). Due to its higher potential, FVca was further characterized, revealing a rich profile of essential amino acids, low-molecular-weight peptides, and a diverse phenolic profile, dominated by phloroglucinol (6.23 mg/g). In addition, the FVca hydrolysate demonstrated severe abiotic interference with the redox viability assay at 10 mg/mL in Caco-2 human colorectal adenocarcinoma cell cultures. These findings highlight that combining cellulase and alcalase effectively solubilizes key bioactive compounds, yielding a hydrolysate highly promising for industrial and biotechnological applications.