Loranda Calderón-Zamora

Viroids are the simplest known infectious agents, consisting of noncoding circular RNAs that replicate autonomously in plant hosts while inducing profound and systemic alterations in host biology. This apparent paradox positions viroids as powerful models for understanding how RNA molecules encode biological information independently of protein translation. A hallmark of viroid infection is the production of viroid‐derived small interfering RNAs (vd‐siRNAs) by the host RNA silencing machinery. Here, we propose that vd‐siRNAs function not merely as antiviroid byproducts, but as active effectors that translate RNA structural information into gene regulatory activity. Through sequence complementarity and selective incorporation into Argonaute complexes, vd‐siRNAs influence host gene expression at multiple levels, including transcript abundance, protein accumulation, epigenetic states, and metabolic pathways. Importantly, their effects extend beyond individual targets and are consistent with broader perturbations of interconnected host regulatory networks, potentially contributing to coordinated transcriptional reprogramming and disease‐associated phenotypes. By integrating molecular, transcriptomic, epigenetic, and systems‐level evidence, we propose a “structure‐to‐network” perspective in which viroid RNAs function as minimal informational systems capable of interfacing with complex cellular pathways. Within this context, vd‐siRNAs emerge as mechanistic links between RNA architecture and multiscale biological responses. Finally, we discuss how this framework expands our understanding of RNA‐mediated regulation and highlights the broader regulatory potential of structured noncoding RNAs.

Glaucoma is conventionally characterized as an intraocular pressure‐dependent optic neuropathy; however, emerging evidence features glaucoma as a complex neurodegenerative disorder of the central nervous system, closely linked to systemic physiological dysregulation. This review aims to combine a rapidly expanding frontier in vision research: the integration of neurotrophic signaling, sleep architecture, and retinal neuroprotection. Neurotrophic factors, particularly the brain‐derived neurotrophic factor‐TrkB axis, are indispensable for the survival and synaptic integrity of retinal ganglion cells. In glaucoma, mechanical and metabolic stressors disrupt the retrograde axonal transport of these survival signals. Furthermore, recent paradigms reveal that neurotrophin expression and downstream signaling cascades are highly modulated by sleep‐wake cycles and circadian rhythms. Sleep fragmentation and chronic sleep disorders, such as obstructive sleep apnea, not only suppress central and ocular neurotrophin synthesis but also exacerbate neuroinflammation, trigger microglial activation, and induce nocturnal ocular perfusion pressure fluctuations. Moreover, the newly characterized ocular glymphatic system shows a highly sleep‐dependent waste clearance mechanism, where sleep deprivation compromises the elimination of neurotoxic aggregates from the optic nerve head. Rather than summarizing this previously separate literature in parallel, this review synthesizes them into a single causal context, explicitly graded by the level of evidentiary certainty, and extends this basis to the clinical dimension of retinal ganglion cell‐related mood disturbance. By integrating these distinct fields, this review proposes an interconnected pathophysiological loop where sleep disturbances diminish neurotrophic support and impair metabolic clearance, rendering retinal ganglion cells highly vulnerable to glaucomatous degeneration. Finally, this review will discuss the therapeutic implications of this network, highlighting chronotherapeutic optimization of intraocular pressure‐lowering agents, small‐molecule TrkB agonists, and targeted sleep interventions as novel, adjuvant neuroprotective strategies. Ultimately, bridging sleep science and sensory neuroscience offers a promising, holistic framework for preserving vision in glaucoma patients.

This study examined how residents of Culiacán, México, adapted over time to prolonged community violence and perceived insecurity. We evaluated a two-speed adaptation theory, which proposes that indicators of acute psychological distress and economic strain decline over time, whereas protective behavioral responses persist as a state of chronic vigilance. A mixed-longitudinal design was employed, consisting of a baseline survey of 1163 residents conducted in October 2024 and a longitudinal cohort of 100 participants followed in February and June 2025. Longitudinal changes were evaluated using Cochran’s Q tests with exact McNemar post hoc comparisons, proportions were reported with 95% Clopper–Pearson confidence intervals, and multivariable logistic regression was used to examine predictors of migration intent. Pharmacologic treatment utilization declined significantly from 36% to 20%, and reported economic strain decreased from 62% to 35% over the study period. In contrast, behavioral routine modifications remained persistently high, decreasing only from 95% to 88%, with no statistically significant longitudinal change. These findings are consistent with the proposed theory, suggesting that while acute psychosocial and economic impacts may diminish over time, protective behavioral adaptations remain comparatively stable. Regarding migration intent, individual economic strain was not significantly associated with the intention to leave the city. Instead, participants who attributed insecurity primarily to social contract collapse, conceptualized as the perceived erosion of community trust, institutional legitimacy, social polarization, and the breakdown of social order, had substantially greater odds of reporting migration intent than those primarily concerned with economic factors (OR = 11.56, 95% CI 1.55–85.98). Overall, these findings suggest that prolonged community violence produces distinct trajectories of psychosocial adaptation, in which acute distress decreases while chronic vigilance persists. Furthermore, migration intentions appear to be more strongly associated with perceived deterioration of the social environment than with individual economic hardship, highlighting the importance of restoring community trust and institutional legitimacy alongside traditional public health and economic interventions.

Background: The chromosomal microdeletion syndrome 2q13 is characterized by craniofacial dysmorphism, developmental delay, intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, cardiac abnormalities, and seizures. Case Presentation: In this study, we present a descriptive genomic observation of a teenage boy presenting with epilepsy, intellectual disability, and mild facial dysmorphism, found to carry a 48.55 kb 2q13 microdeletion restricted to the BUB1 locus alongside a concurrent 11q21 microdeletion. While his clinical features overlap with the 2q13 microdeletion spectrum, the exact pathogenic contribution of each variant remains a subject of hypothesis due to the lack of parental inheritance data. Conclusions: Further research is necessary to ascertain the impact of the concurrence of small deletions on these disorders. This case underscores the clinical complexity introduced by compound minor copy number variations and emphasizes the value of molecular cytogenetics in evaluating idiopathic neurodevelopmental disorders.

Background/Objectives: The Diabetes-Specific Dementia Risk Score (DSDRS) integrates clinical and metabolic markers to predict cognitive decline in Type 2 diabetes mellitus (T2DM), yet its association with key modifiable risk factors remains unvalidated in Latin American cohorts. This study aimed to assess the relationship between the DSDRS and clinical, biochemical, anthropometric, and neuropsychological variables in older adults with T2DM. Methods: A cross-sectional study of 291 Mexican adults aged ≥ 60 with T2DM was conducted, including assessments of cognitive function (MoCA), depression (BDI), sleep quality (AIS), and metabolic parameters. Results: Higher DSDRS correlated with lower cognitive scores, poorer sleep quality, reduced muscle mass, and smoking status. Multiple regression explained 32% of DSDRS variance, highlighting these factors as significant contributors. Conclusions: The DSDRS reflects multifactorial influences on dementia risk in older adults with T2DM and may aid early identification of individuals at increased cognitive vulnerability in this population.

Background: Individuals with Down syndrome (DS) face a high burden of health complications, yet the molecular underpinnings remain incompletely defined. Objective: The objective of this study is to systematically identify metabolomic changes in individuals with DS and how they relate to DS‐associated conditions. Methods: A scoping review of the literature was performed across four online databases to identify studies profiling metabolites in people with DS using untargeted or targeted metabolomics procedures. The findings were narratively synthesised to provide a comprehensive overview of patterns of convergence and variability across studies. Results: Thirty‐four studies examining metabolites in individuals with DS were identified. The combined findings revealed widespread disruptions in energy (e.g., tricarboxylic acid cycle intermediates and acylcarnitines), one‐carbon (e.g., methionine and the SAM/SAH axis), amino acid (e.g., tryptophan‐kynurenine and glutamate/GABA) and lipid (e.g., phospholipids and sphingolipids) metabolism, along with changes in immune and neurotransmitter pathways. These metabolic alterations are associated with phenotypic variability and comorbidities in DS. However, the evidence reflects partially convergent and context‐dependent patterns, with substantial variability across studies. Conclusion: Metabolic disturbances are common in DS, suggesting candidate metabolic signatures that still require independent replication and validation. Current evidence is predominantly cross‐sectional and associative, limiting causal inference. Integrating metabolomics with multi‐omics approaches may enhance the understanding of DS‐related health issues and support future translation into clinical applications.

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this in silico study, we characterized metabolites putatively annotated by UPLC-ESI-HRMS and evaluated their predicted ACE inhibitory potential. We performed molecular docking with AutoDock 4 and assessed pharmacokinetic and toxicological properties using the SwissADME, PASS, and ProTox platforms. Several metabolites showed favorable binding orientations within the ACE catalytic pocket, including interactions with key residues and proximity to the zinc-binding motif. Lehualide G, Val–Asn–Pro, tanariflavanone B, hydroxyterbinafine, and anhydro-vitamin A exhibited the most favorable docking profiles. PASS predictions indicated vascular-related bioactivity signals for selected compounds, whereas ADMET modeling revealed heterogeneous but classifiable pharmacokinetic and safety characteristics. The convergence of predicted binding compatibility, bioactivity signals, and stratified safety margins supports P. tricornutum as a promising source of candidate molecules for further experimental validation in antihypertensive research.

The continuous emergence of SARS-CoV-2 variants highlights the need for novel antiviral agents with favorable safety profiles. Marine microalgae constitute a valuable source of bioactive compounds, including antiviral peptides. Building on previous in silico identification of peptides derived from the marine microalga Phaeodactylum tricornutum with predicted activity against SARS-CoV-2, this study evaluated the antiviral capacity of peptide fractions generated by enzymatic hydrolysis and separated by molecular weight (10–30, 5–10, 3–5, and P. tricornutum–derived peptide fractions as marine antiviral candidates and supports the integration of in silico and functional approaches for marine drug discovery.

Introduction: Down syndrome (DS) is linked to increased risks of metabolic, gastrointestinal, and neurodegenerative disorders. Early alterations in the gut microbiota have potential long‐term health impacts. This report appears to be the first study to stratify DS participants by age to explore early‐life microbiota changes. Methodology: We conducted a cross‐sectional analysis of gut microbiota in children, adolescents, and adults with DS, compared with a control group, using Illumina iSeq100 sequencing of the V4 polymorphic region of the 16S rRNA gene. Results: Children with DS exhibited lower microbial diversity and a higher abundance of genera such as Sutterella and Enterococcus . These differences lessened in older groups, indicating a convergence with control profiles. Conclusion: Early alterations in gut microbiota in DS may contribute to metabolic and neurodegenerative risks, emphasizing the need for early interventions to potentially improve long‐term health outcomes.

Introduction: Type 2 diabetes mellitus (T2DM) is known to increase the risk of Alzheimer’s disease (AD), but the role of the gut microbiota in this relationship is not fully understood. This study investigated the gut microbiota profiles of adults with T2DM, adults with AD, both conditions (AD–T2DM), and healthy controls to identify patterns associated with metabolic and neurodegenerative conditions. Methods: A cross‐sectional study was conducted with 148 participants divided into six groups: CTRL < 60 years, CTRL ≥ 60 years, T2DM < 60 years, T2DM ≥ 60 years, AD, and AD–T2DM. Clinical assessments and 16S rRNA gene sequencing of fecal samples were performed to analyze microbial diversity and composition. Results: Compared with controls, older adults with T2DM, AD, and AD–T2DM presented reduced microbial diversity and distinct microbial compositions. Notably, SCFA‐producing genera ( Veillonella and Dialister ) decreased in T2DM patients ≥ 60 years, whereas Roseburia and Blautia were more abundant in AD patients and those with AD–T2DM . GDP‐mannose biosynthesis was downregulated in AD–T2DM patients. Conclusion: This study highlights changes in the microbiota in T2DM and AD–T2DM patients, suggesting that targeting these microbial alterations could offer new prevention strategies for metabolic‐neurodegenerative comorbidities. Significance Statement: T2DM and AD share metabolic and inflammatory pathways, yet their combined impact on the gut microbiota remains unexplored. By profiling 148 adults, healthy individuals, those with T2DM, AD, and co‐occurring AD–T2DM, using 16S rRNA gene V4 region sequencing, we identified specific dysbiosis in AD–T2DM. Rather than examining T2DM and AD as independent conditions, the present study conceptualizes their coexistence as a metabolic–neurodegenerative interaction state and assesses whether this comorbidity is associated with a distinct gut microbiota composition and predicted functional profile. Therefore, we examine the gut microbiota of adults with AD–T2DM using an age‐stratified design in an underrepresented Mexican population, integrating clinical, metabolic, cognitive, taxonomic, and functional data to explore potential mechanisms underlying metabolic–neurodegenerative crosstalk. These findings identify microbial genera that may mediate the “diabeto‐neuro” crosstalk, offering novel targets for early intervention and precision microbiota‐based therapies to mitigate metabolic‐neurodegenerative comorbidity.