Fundación Ciencia and Vida

Propolis is a chemically complex natural product with recognized antioxidant potential, but its compositional heterogeneity and poor aqueous solubility complicate formulation and interpretation of in vitro release behavior. In this study, a nanostructured lipid carrier (NLC) based on Gelucire® 44/14 was developed as a physicochemical platform to modulate the accessibility of a selected Chilean ethanolic propolis extract. Propolis extracts from different origins were first screened using complementary antioxidant assays (DPPH, ABTS, ORAC, FRAP), leading to the selection of the Peñaflor extract, which exhibited the highest phenolic content (~41 mg GAE/g) and antioxidant capacity. The selected extract was incorporated into NLCs with encapsulation efficiencies above 90%, a narrow size distribution (~200 nm), and high stability over 90 days. Under simple aqueous conditions, propolis release remained limited (<15% over 6 h), consistent with diffusion- and partition-controlled transport. In simulated gastrointestinal media containing bile components, pronounced pH- and composition-dependent effects were observed. While fed-state intestinal conditions induced extensive morphological remodeling without increasing the analytically accessible fraction (<3% at 4 h), fasted-state intestinal media promoted a higher accessible fraction (~14% within 1 h) without complete carrier disruption, as confirmed by transmission electron microscopy. Preliminary cytocompatibility studies in HepG2 cells showed acceptable viability at 10-40 µg/mL and concentration-dependent effects at higher doses. Overall, this work demonstrates that bile components modulate propolis accessibility through dynamic partitioning and colloidal reorganization rather than simple carrier breakdown, providing a physicochemical framework for future digestion and absorption studies.

ABSTRACT Trypanosomatid parasites of the genus Leishmania rely on post-transcriptional regulation of gene expression because gene transcription is not canonically regulated at the single-gene level. RNA-binding proteins (RBPs) are central to this regulatory architecture, yet their genome-wide diversity, conservation, and condition-specific associations remain incompletely defined across the genus. Here, we combined comparative genomics and systems-level transcriptomic analyses to map the RBP repertoire in 33 strains spanning 19 Leishmania species. We also connect RBPs to developmental, stress, and drug-resistance contexts, using Leishmania braziliensis as an example. Using probabilistic domain detection and homology-based annotation, we identified 38,662 putative RBPs across all genomes, with 1,114 to 1,491 RBPs per genome. Comparative genomics analysis revealed a conserved core of 404 RBP clusters shared across all examined species, alongside lineage-restricted clusters in major Leishmania groups. We notably detected widespread conservation of enzymes linked to messenger RNA modification (for example, NAT10, TRMT6/61A, and NSUN2), but failed to identify canonical N6-methyladenosine writer orthologs, suggesting divergence of this machinery across Leishmania genomes. In L. braziliensis , expression profiling in different life-cycle stages and stress conditions highlighted stage-biased RBPs, including elevated ZC3H20 in amastigotes and increased RBP6 in metacyclic promastigotes. Finally, co-expression network analysis of trivalent antimony (SbIII) resistant genotypes identified RBPs co-expressed with genes previously associated with antimony resistance. In contrast, motif-based analysis supported a putative DRBD3-centered post-transcriptional module that includes 10 candidate stabilized transcripts in SbIII-resistant promastigotes. Together, these results provide a comparative framework to prioritize RBPs and associated regulatory programs implicated in parasite adaptation and antimony resistance. AUTHOR SUMMARY Leishmaniasis results from infection by Leishmania parasites and remains challenging to control due to limited treatments and the continual emergence of drug resistance, especially to antimonials. These parasites exhibit an unusual gene regulation method; instead of activating or deactivating transcription for individual genes, they depend heavily on proteins that bind RNA to determine which messages are retained, translated, or degraded. In this study, we created a comprehensive atlas of RNA-binding proteins across the Leishmania genus by analyzing 33 parasite strains from 19 species. We identified a large core set of conserved RNA-binding proteins shared by all species, along with lineage-specific proteins that may help different parasite groups adapt to various hosts and environments. Additionally, we mapped enzymes responsible for RNA chemical modifications and found that the typical machinery for m6A marks in many organisms appears to be divergent in Leishmania . Finally, by associating RNA-binding proteins with specific life-cycle stages, stress responses, and antimony resistance in L. braziliensis , we pinpointed candidate regulators and gene modules for further experimental validation. This resource helps prioritize regulatory factors that could drive parasite adaptation and resistance.

Plasma biomarkers have emerged as robust indicators of Alzheimer's disease (AD) pathology, offering accessible tools for staging and stratification. However, their expression across globally diverse populations remains poorly characterized. The aim of this study was to evaluate whether the combination of plasma biomarkers could distinguish different stages along the AD continuum and assess their clinical associations in a Latin American cohort. We evaluated plasma amyloid, tau, and neurodegeneration (ATN) biomarkers in 318 older adults from a Chilean community- and clinic-based cohort, including individuals with subjective cognitive complaints (SCC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (ADD), alongside cognitively unimpaired (CU) participants. Plasma ATN biomarkers (Aβ42/Aβ40, p-tau217, NfL, and GFAP) were quantified using Simoa technology. Global cognition was assessed with the Addenbrooke's Cognitive Examination (ACE), memory with the Free and Cued Selective Reminding Test (FCSRT), and functional ability with the Technology-Activities of Daily Living Questionnaire (T-ADLQ). Group differences in plasma biomarkers were examined using ANCOVA models adjusted for age, sex, and education, and associations with cognitive performance were evaluated through linear regression analyses. In addition, supervised machine-learning models were implemented to classify participants across diagnostic categories based on plasma biomarker profiles, using cross-validation to evaluate predictive performance. We observed a progressive decline in the Aβ42/Aβ40 ratio and elevations in p-tau217 and GFAP across the clinical continuum. Additionally, p-tau217 and NfL levels were inversely associated with cognitive, memory, and functional performance. Notably, p-tau217 distinguished ADD from CU with high accuracy (AUC = 0.88), although its performance in earlier stages was limited. These findings support the biological consistency of plasma biomarkers in AD-related neurodegeneration and provide novel evidence from a Latin American population. Further studies are needed to improve early-stage detection and to better understand how genetic, environmental, and health factors shape biomarker expressions in underrepresented regions.

The worldwide rise of neurological and psychiatric conditions poses major challenges. However, current global research remains fragmented, dominated by limited cohorts and poorly integrated datasets that disconnect whole-body health, exposome, and brain health. Theories rarely unify brain measures with extracerebral factors or capture heterogeneity in individual trajectories. We introduce multimodal diversity, a non-linear, non-simplistic causal and ecological construct integrating data representation, whole-body and exposomic factors, and computational modeling to address this situated, embedded, and embodied complexity. This heuristic metamodel integrates global, multilevel data into personalized predictions fostering population inclusion, multimodal integration, diagnostic precision, and equitable, context-sensitive advances in brain health.

In today’s digital era, the internet offers unprecedented access to information, but it also accelerates the spread of misinformation. Nowhere is this more problematic than in public health, as the COVID-19 pandemic clearly demonstrated. Misinformation can erode trust in science and health authorities, leading people to disregard expert guidance and adopt unverified treatments that endanger population health. We examine how misinformation alters the course of an infectious disease outbreak by modeling the simultaneous uptake of preventive measures and engagement in harmful behaviors. The model captures the competing influences of accurate information and misinformation on individual decision making. Our results show that even a modest influx of misinformation can greatly amplify disease transmission, deepening the epidemic’s severity. These findings highlight the urgent need for robust strategies to curb misinformation and support public health interventions during health crises.

The vaginal microbiota plays a critical role in maintaining reproductive health. Although Lactobacillus species often dominate the vaginal environment in healthy individuals, recent studies have shown that healthy microbiota compositions can also include Lactobacillus-depleted states, as described by the Community State Types (CSTs) framework. However, disruptions in the microbiota composition, such as those caused by sexually transmitted infections (STIs), can lead to increased diversity and instability, compromising host protection. This study investigates the association between vaginal microbiota composition and the prevalence of STIs in a cohort of incarcerated women in Chile. Using metataxonomic approaches targeting 16S and 18S rRNA genes, we characterized prokaryotic and eukaryotic components of the vaginal microbiota across healthy, dysbiotic, and pathogen-dominated subjects. Alpha diversity analysis using the Shannon index indicated that Lactobacillus-dominant communities were associated with lower microbial diversity correlates with reduced variability. Whereas communities dominated by pathogens including Trichomonas vaginalis, Gardnerella vaginalis, Treponema pallidum, and HIV, tended to exhibit higher diversity. The pathogen-dominated group displayed an increased prevalence of opportunistic microorganisms and reduced Lactobacillus abundance, which may reflect an imbalance in the microbial ecosystem, often interpreted as reduced stability. This study provides novel insights into the intricate dynamics between normal and altered vaginal microbiomes and their association with STIs. Understanding these community-level patterns and associations is crucial for designing targeted interventions aimed at restoring microbial balance and preventing infections.

Autophagy deficiency in breast cancer promotes metastasis through the accumulation of the autophagy cargo receptor NBR1. Here we show that autophagy normally suppresses breast cancer metastasis by enabling the clearance of NBR1-p62/SQSTM1 complexes that instruct p63-mediated pro-metastatic basal differentiation programmes. When autophagy is inhibited, the autophagy cargo receptors NBR1 and p62/SQSTM1 accumulate within biomolecular condensates in cells, which drives basal differentiation in both mouse and human breast cancer models. Mechanistically, these NBR1-p62/SQSTM1 complexes sequester ITCH, a ubiquitin ligase that degrades and negatively regulates p63 in breast cancer cells, thereby stabilizing and activating p63. Accordingly, mutant forms of NBR1 unable to sequester ITCH into NBR1-p62/SQSTM1 complexes do not promote basal differentiation and metastasis in vivo. Overall, our findings illuminate how proteostatic defects arising in the setting of therapeutic autophagy inhibition modulate epithelial lineage fidelity and metastatic progression.

Leishmania spp. is the etiological agent of leishmaniases, neglected diseases that seek to be eradicated in the coming years. The life cycle of these parasites involves different host and stress environments. In recent years, many studies have shown that several protein-coding genes are directly involved with the development and host interactions. However, little is still known about the role of non-coding RNAs (ncRNAs) in life cycle progression. In this study, we aimed to identify the genomic structure and function of ncRNAs from Leishmania spp. and to get insights into the repertoire of ncRNAs (RNAome) of this protozoan genus. We studied 26 strains corresponding to 16 different species of Leishmania. Our RNAome analysis revealed the presence of several ncRNAs that are shared among different species, allowing us to differentiate between subgenera as well as between species that are canonically related to visceral leishmaniasis. We also studied co-expression relationships between coding genes and ncRNAs which in the amastigote developmental stage for Leishmania braziliensis and Leishmania donovani revealed the presence of miRNA-like transcripts co-expressed with several coding genes involved in starvation, survival and histone modification. This work represents the first effort to characterize the Leishmania ssp. RNAome, supporting further approaches to better understand the role of ncRNAs in gene regulation, infective process, and host-parasite interaction.