Search Results (157)

Background/Objectives: Global warming and rising CO₂ concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to warming and elevated CO₂ on progeny physiology, genetic diversity, and population structure in Stylosanthes capitata, a resilient forage legume native to Brazil. Methods: Maternal plants were cultivated under controlled treatments, including ambient conditions (control), elevated CO₂ at 600 ppm (eCO₂), elevated temperature at +2 °C (eTE), and their combined exposure (eTEeCO₂), within a Trop-T-FACE field facility (Temperature Free-Air Controlled Enhancement and Free-Air Carbon Dioxide Enrichment). Seed traits (seeds per inflorescence, hundred-seed mass, abortion, non-viable seeds, coat color, germination at 32, 40, 71 weeks) and abnormal seedling rates were quantified. Genetic diversity metrics included the average (A) and effective (Ae) number of alleles, observed (Ho) and expected (He) heterozygosity, and inbreeding coefficient (Fis). Population structure was assessed using Principal Coordinates Analysis (PCoA), Analysis of Molecular Variance (AMOVA), number of migrants per generation (Nm), and genetic differentiation index (Fst). Two- and three-way Analysis of Variance (ANOVA) were used to evaluate factor effects. Results: Compared to control conditions, warming increased seeds per inflorescence (+46%), reduced abortion (−42.9%), non-viable seeds (−57%), and altered coat color. The germination speed index (GSI +23.5%) and germination rate (Gr +11%) improved with warming; combined treatments decreased germination time (GT −9.6%). Storage preserved germination traits, with warming enhancing performance over time and reducing abnormal seedlings (−54.5%). Conversely, elevated CO₂ shortened GSI in late stages, impairing germination efficiency. Warming reduced Ae (−35%), He (−20%), and raised Fis (maternal 0.50, progeny 0.58), consistent with the species’ mixed mating system; A and Ho were unaffected. Allele frequency shifts suggested selective pressure under eTE. Warming induced slight structure in PCoA, and AMOVA detected 1% (maternal) and 9% (progeny) variation. Fst = 0.06 and Nm = 3.8 imply environmental influence without isolation. Conclusions: Warming significantly shapes seed quality, reproductive success, and genetic diversity in S. capitata. Improved reproduction and germination suggest adaptive advantages, but higher inbreeding and reduced diversity may constrain long-term resilience. The findings underscore the need for genetic monitoring and broader genetic bases in cultivars confronting environmental stressors. Full article

The study’s aim was to evaluate electroretinographic (ERG) alterations in Fragile X syndrome (FXS), FMR1 premutation carriers, and controls, and to explore correlations with peripheral blood FMRP expression levels and behavioral outcomes. ERG recordings were obtained using a handheld device across three stimulus protocols in 43 premutation carriers, 39 individuals with FXS, and 23 controls. Peripheral blood FMRP expression levels were quantified using TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer). Correlations were assessed with cognitive and behavioral measures including IQ (Intelligence Quotient), ABC_FX (Aberrant Behavior Checklist for Fragile X Syndrome), SNAP-IV (Swanson, Nolan, and Pelham Teacher and Parent Rating Scale), SEQ (Sensory Experiences Questionnaire), ADAMS (Anxiety, Depression, and Mood Scale), and the Vineland III Adaptive Behavior Scale standard score. Significant group differences were observed in multiple ERG parameters, particularly in 2 Hz b-wave amplitude (p = 0.0081), 2 Hz b-wave time to peak (p = 0.0164), 28.3 Hz flash combined amplitude (p = 0.0139), 3.4 Hz red/blue flash b-wave amplitude (p = 0.0026), and PhNR amplitude (p = 0.0026), indicating both outer and inner retinal dysfunction in FXS and premutation groups. Despite high test–retest reliability for ERG (ICC range = 0.71–0.92) and FMRP (ICC = 0.70), no correlation was found between ERG metrics and FMRP or behavioral measures. However, FMRP levels strongly correlated with IQ (ρ = 0.69, p < 0.0001) and inversely with behavioral impairment [ABC_FX (ρ = −0.47, p = 0.0041), SNAP-IV (ρ = −0.48, p = 0.0039), SEQ (ρ = −0.43, p = 0.0146), and the Vineland III standard score (ρ = 0.56, p = 0.0019)]. ERG reveals distinct retinal functional abnormalities in FMR1-related conditions but does not correlate with peripheral FMRP expression levels, highlighting the need for multimodal biomarkers integrating radiological, physiological, behavioral, and molecular measures. Full article

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes. Full article

Accessible tools for post-stroke motor rehabilitation are critically needed to promote recovery beyond clinical settings. This pilot study evaluated the impact of a posture correction intervention using the Postural SmartVest, a wearable device that delivers multisensory feedback via a smartphone app. Forty individuals with post-stroke hemiparesis participated in a single supervised session, during which each patient completed the same four-phase functional protocol: multidirectional walking, free walking toward a refrigerator, an upper-limb reaching and object-handling task, and walking back to the starting point. Under the supervision of their therapists, each patient performed the full protocol twice—first without feedback and then with feedback—which allowed within-subject comparisons across multiple metrics, including upright posture duration, number and frequency of posture-related events, and temporal distribution. Additional analyses explored associations with demographic and clinical variables and identified predictors through regression models. Wilcoxon signed-rank and Mann–Whitney U tests showed significant improvements with feedback, including an increase in upright posture time ($p<0.001$), an increase in the frequency of upright posture events ($p<0.001$), and a decrease in the total task time ($p=0.038$). No significant subgroup differences were found for age, sex, lateralization, or stroke chronicity. Regression models did not identify significant predictors of improvement. Full article

Fragile X syndrome is characterized by the diminished expression of the fragile X messenger ribonucleoprotein (FMRP), a ubiquitously expressed RNA binding protein with numerous functions in cells. Our prior work found significant differences in physiological and behavioral outcomes as a function of FMRP levels and in response to diet in mice. Here, we assess protein biomarker levels as a function of FMRP levels, sex and matched casein and soy protein isolate-based purified ingredient diets in Fmr1^KO and littermate mice. Brain regions (cortex, hippocampus, and hypothalamus) and blood plasma were analyzed by RayBiotech’s Quantibody^® Mouse Cytokine Antibody Array 640 to quantitate the expression of 640 proteins. The main findings were the identification of numerous proteins that were differentially expressed in response to diet, sex and/or genotype. Of note, prolactin (PRL) levels in blood plasma were significantly elevated in Fmr1^KO female mice as a function of genotype and sex selectively with the AIN-93G/casein diet. Also, using a moderately stringent significance cutoff, growth differentiation factor 9 (GDF-9) in plasma from mice fed AIN-93G/soy was the only protein studied by Quantibody arrays that was differentially expressed between WT and Fmr1^KO male mice. When comparing the results from a pelleted infant formula study with AIN-93G-based diets, insulin-like growth factor binding protein 5 (IGFBP5) in plasma was the only protein differentially expressed as a function of soy in the diet. There was no overlap in statistically significant results when comparing tissue analyzed by mass spectrometry versus Quantibody arrays from mice maintained on AIN-93G-based diets. In conclusion, gene–diet interactions affect protein expression in Fmr1^KO and littermate mice and need to be considered in study design. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized advanced melanoma treatment, yet many patients fail to achieve sustained clinical benefit. Several biomarkers, including tumor microenvironment (TME) signature, PD-1/PD-L1 expression, and IFN-γ signaling, have been proposed. However, robust predictive markers remain elusive. This study aimed to identify molecular markers of response by analyzing tumor and peripheral immune signatures. Methods: This study analyzed 21 advanced melanoma patients treated with ICIs. Formalin-fixed, paraffin-embedded tumors underwent RNA-sequencing targeting 1392 immuno-oncology probes. Genes significantly associated with progression-free survival (PFS) by log-rank test underwent hierarchical clustering analysis (HCA). Differential expression and xCell analyses were then performed on the resulting clusters. Cox multivariate analysis was applied to identify independent PFS predictors. Pre-treatment peripheral blood mononuclear cells were analyzed by mass cytometry, followed by FlowSOM and UMAP clustering. Results: Fifty-five genes significantly associated with PFS identified two molecular clusters via HCA. Cluster A demonstrated prolonged PFS (59.4 vs. 2.4 months, p = 0.0004), while Cluster B was characterized by downregulated IFN-γ signaling, antigen presentation pathways, and reduced immune score. Multivariate Cox analysis confirmed molecular cluster as an independent PFS predictor (p < 0.001). Mass cytometry revealed higher frequencies of circulating PD-1+ CD4+ effector memory (EM) T subpopulations among responders. Conclusions: This study highlights the potential role of molecular and immune profiling in predicting ICI response in advanced melanoma. The identification of distinct molecular clusters underscores significant TME heterogeneity, with immune-cold tumor clusters associated with poorer outcomes. Furthermore, circulating PD-1+ T subpopulations emerged as potential markers of ICI response, suggesting their value in improving patient stratification. Full article

The Fragile X Mental Retardation 1 (FMR1) gene is well-known for its role in Fragile X syndrome, a neurodevelopmental disorder, but emerging evidence suggests its involvement in regulating cellular metabolism, with implications for cancer biology. FMR1 encodes the Fragile X mental retardation protein (FMRP), an RNA-binding protein that controls various cellular processes, including translation, synaptic plasticity, and RNA metabolism. Recent studies have uncovered novel links between FMR1, metabolic regulation, and tumorigenesis. This review discusses the role of FMR1 in cellular metabolism and its potential involvement in cancer, focusing on glycolysis, mitochondrial metabolism, lipid metabolism, immune cell metabolism, and tumor immune evasion, and as a potential target to enhance immunotherapy, and highlights future research directions to elucidate its mechanistic roles in cancer. Full article

Tau protein plays a pivotal role in maintaining neuronal structure and function through its regulation of microtubule stability and neuronal polarity. Encoded by the MAPT gene, Tau exists in multiple isoforms due to alternative mRNA splicing, with differential expression in the central and peripheral nervous systems. In healthy neurons, tau mRNA is selectively localized and translated in axons, a process tightly regulated by untranslated regions (UTRs) and RNA-binding proteins such as HuD and FMRP. Pathologically, Tau undergoes hyperphosphorylation, misfolding, and aggregation, which contribute to neurodegeneration in a range of disorders collectively known as tauopathies. Alzheimer’s disease (AD) is the most prevalent tauopathy, where abnormal Tau accumulation in the temporal and frontal lobes correlates with cognitive decline and behavioral symptoms. Other tauopathies, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Frontotemporal Dementia with Parkinsonism (FTDP-17), and Pick’s disease, are distinguished by the predominance of specific Tau isoforms (3R or 4R), cellular distribution, and affected brain regions. Notably, astroglial tauopathies highlight the pathological role of Tau accumulation in glial cells, expanding the understanding of neurodegeneration beyond neurons. Despite advances in imaging biomarkers (e.g., Tau-PET) and molecular diagnostics, effective disease-modifying therapies for tauopathies remain elusive. Ongoing research targets Tau through immunotherapies, splicing modulators, kinase inhibitors, and antisense oligonucleotides, aiming to mitigate Tau pathology and its deleterious effects. Understanding the multifaceted roles of Tau in neuronal and glial contexts is critical for developing future therapeutic strategies against tauopathies. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19. Full article

Different treatments have been proposed for morphofunctional bone repair; however, they are not always efficient and have limitations. In this experimental study, we present matrix composites with a possible synergistic effect acting with scaffolds for bone growth and use of photobiomodulation (PBM) to accelerate this tissue repair. Thus, the objective was to evaluate the effect of PBM in the repair of a long bone (tibia) of rats filled with biomimetic collagen matrices with nanohydroxyapatite and heterologous fibrin biopolymer (FB). Forty-eight rats were distributed into eight groups (n = six each): Blood Clot (BC), Blood Clot + PBM (BCP), Matrix (M), Matrix + PBM (MP), Fibrin Biopolymer (FB), Fibrin Biopolymer + PBM (FBP), Matrix + FB (MFB), Matrix + FB + PBM (MFBP). A 2.0 mm bone defect was created in the proximal third of the left tibia. The BCP, MP, FBP, and MFBP groups underwent PBM during surgery and maintained twice a week until euthanasia at 42 days. Microcomputed tomography (micro-CT), histomorphological and histomorphometric analyses were performed. Micro-CT analysis revealed that PBM influenced cortical interposition between the remnant and newly formed bone. Histologically, no exacerbated inflammatory focus or foreign body-type granulomatous reaction was observed in any group; however, a vast collagenous matrix with a more oriented and thicker spatial conformation was observed in the PBM-treated groups. Histomorphometrically, the BCP, MP, and MFBP groups showed significantly higher values compared to the other groups. Specifically, the BC group presented a mean bone tissue density of 68.33 ± 7.394, while the BCP and MP groups showed 99.83 ± 11.87 and 99.67 ± 20.58, respectively (p < 0.05). Qualitative analysis of collagen fibers indicated enhanced organization and maturation in PBM-treated groups. This study concluded that the association of PBM in the repair of long bones in rats, filled with biomimetic collagen matrices with nanohydroxyapatite and fibrin biopolymer, presented results that contribute to the improvement of bone growth, together with the association of scaffolds. Full article

Background/Objectives: Anadenanthera colubrina (popularly known as angico; in this study: Acol) is a bee-pollinated tree with gravity-dispersed seeds that occurs in dry tropical forests (SDTF), one of the most fragmented tropical ecosystems. In this study, we analyzed the resilience of 30 Acol Forest fragments of Ribeirão Preto, São Paulo, Brazil, and the flow of pollinators among these fragments based on the flight ranges of Apis mellifera (6 km) and Trigona spinipes (8 km). Additionally, we investigated genetic diversity, spatial genetic structure (SGS), and phenology across generations of one Acol population (AcolPM), located in the urban fragment M103 in the “Parque Municipal Morro de São Bento” (a municipal park in Ribeirão Preto). Methods: We mapped Acol fragments using geospatial data, with relief and slope analysis derived from digital terrain modeling. We created a flow diagram based on the pollinator’s flight ranges and calculated betweenness centrality. We amplified DNA from AcolPM individuals using 14 SSR molecular markers. Results: Notably, 17 of the 30 fragments occurred on slopes > 12%, terrain unsuitable for agriculture or construction, indicating that the presence of A. colubrina may serve as an indicator of territorial transformations. The AcolPM population (Fragment M103) emerged as a key node among the angicais, connected by the native pollinator T. spinipes, being fundamental for regional gene flow. In this focal population, we observed a slight but significant inbreeding (Fis, Fit, p < 0.01) and an SGS up to ~17 m. Genetic diversity was intermediate (He ≈ 0.62), and PCoA, Fst, and AMOVA values suggest low generational isolation, with most genetic variation within generations. This highlights AcolPM as a promising source for seed collection for reforestation. Phenological observations showed that fructification occurs between September and October, at the beginning of the rainy season. Conclusions: We concluded that Acol resilience is linked to the species’ mixed-mating system and pollinator dynamics-driven connectivity, allowing for the maintenance of genetic diversity in fragmented landscapes, as well as its natural tendency to form dense angicais clusters in non-arable slopes. We reaffirmed A. colubrina as a valuable species for restoration and urban climate resilience, providing cooling shade to humans and wildlife alike while offering refuge and food for local insects and birds in a warming landscape. Full article

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic contributor to autism spectrum disorder. It is caused by a CGG trinucleotide repeat expansion in the FMR1 gene, resulting in gene silencing and the loss of FMRP, an RNA-binding protein essential for synaptic plasticity. This review covers over 80 years of FXS research, highlighting key milestones, clinical features, genetic and molecular mechanisms, the FXS mouse model, disrupted molecular pathways, and current therapeutic strategies. Additionally, we discuss recent advances including AI-driven combination therapies, CRISPR-based gene editing, and antisense oligonucleotides (ASOs) therapies. Despite these scientific breakthroughs, translating preclinical findings into effective clinical treatments remains challenging. Clinical trials have faced several difficulties, including patient heterogeneity, inconsistent outcome measures, and variable therapeutic responses. Standardized preclinical testing protocols and refined clinical trial designs are required to overcome these challenges. The development of FXS-specific biomarkers could also improve the precision of treatment assessments. Ultimately, future therapies will need to combine pharmacological and behavioral interventions tailored to individual needs. While significant challenges remain, ongoing research continues to offer hope for transformative breakthroughs that could significantly improve the quality of life for individuals with FXS and their families. Full article

We investigated the molecular and clinical profile of five boys carrying the fragile X messenger ribonucleoprotein 1 (FMR1) mutation and who suffered from the effects of prenatal alcohol exposure. Fragile X syndrome (FXS) testing was performed using PCR and Southern Blot analysis, and fragile X messenger ribonucleoprotein protein (FMRP) expression levels were measured by Western blot analysis. Clinical evaluation included cognitive functions, adaptive skills, autism phenotype, and severity of behavior measures. Fetal Alcohol Spectrum Disorder (FASD) was also assessed. Five adopted male siblings were investigated, four of which (cases 1, 2, 3, and 4) were diagnosed with FXS, FASD, and ASD, and one, the fraternal triplet (case 5), was diagnosed with FASD and ASD and no FXS. The molecular profile of case 1 and 2 showed the presence of a hypermethylated full mutation (FM) and the resulting absence of FMRP. Cases 3 and 4 (identical twins) were FM-size mosaics (for the presence of an FM and a deleted allele), resulting in 16% and 50% FMRP expression levels, respectively. FMRP expression level was normal in case 5 (fraternal twin). Severe behavioral problems were observed in all cases, including aggression, tantrum, self-harming, anxiety, and defiant behavior, due to different mutations of the FMR1 gene, in addition to biological exposure, home environmental factors, and potentially to additional background gene effects. Full article

Background: The fragile X protein family comprises three members: the fragile X syndrome protein (FMRP) and its structural homologs, fragile X syndrome 1 and 2 (FXR1 and FXR2). FMRP has a significant role in controlling the genesis and progression of various forms of human cancer. However, studies on the prognostic significance of FXR2 in cancer are scarce. Thus, this study aimed to investigate the clinicopathological significance of FXR2, a member of the FMRP family, in primary breast cancer (BC). Methods: A total of 100 formalin-fixed paraffin-embedded (FFPE) tissue blocks from invasive BC cases were collected from King Abdulaziz Hospital in Saudi Arabia. Immunohistochemistry (IHC) was used to assess FXR2 protein expression in the BC tissues, and the results were correlated with clinicopathological parameters, such as tumor grade, tumor size and hormone receptor status. Additionally, the association between clinicopathological features and FXR2 mRNA expression was assessed using the BC Gene-Expression Miner v5.0 tool on all publicly available DNA microarray (n = 10,872) and RNA sequence (n = 4421) data to validate the results. Results: FXR2 protein expression was significantly associated with human epidermal growth factor 2 (HER2) negativity (p = 0.010) and low Ki67 (p < 0.001). Both DNA microarray and RNA sequence data showed that HER2 negativity was strongly linked to high levels of FXR2 mRNA. High FXR2 mRNA levels were also correlated with hormone receptor negativity and mutated p53. Conclusions: This study suggests that FXR2 may have indirect clinical significance in BC. However, further studies are warranted to deepen our understanding of the association between FXR2 and other clinicopathological parameters, which could lead to improved diagnostic, treatment, and prognostic strategies for BC patients. Full article

Background/Objectives: Fragile X syndrome (FXS) is a disease of pathologic epigenetic silencing induced by RNA. In FXS, an expanded CGG repeat tract in the FMR1 gene induces epigenetic silencing during embryogenesis. FMR1 silencing can be reversed with 5-aza-deoxyctidine (5-aza-dC), a nonspecific epigenetic reactivator; however, continuous administration of 5-aza-dC is problematic due to its toxicity. We describe an approach to restore FMR1 expression in FXS neurons by transient treatment with 5-aza-dC, followed by treatment with 2HE-5NMe, which binds the CGG repeat expansion in the FMR1 mRNA and could block the resilencing of the FMR1 gene after withdrawal of 5-aza-dC. Methods: This study uses immunofluorescence and fluorescent in situ hybridization (FISH) to measure whether FMR1 expression is maintained in FXS post-mitotic neurons treated with 2HE-5NMe. Genome-wide profiling of histone marks was used to monitor epigenetic changes and drug selectivity in response to 5-aza-dC followed by 2HE-5NMe treatment. Changes to dendritic morphology were visualized using confocal microscopy. Results: In this study, we find that 2HE-5Nme maintains FMR1 in a reactivated state after reactivation using 5-aza-dC in post-mitotic neurons. FMR1 reactivation in neurons results in the re-expression of FMRP and reversal of FXS-associated dendritic spine defects. Conclusions: These results demonstrate that an RNA-binding small molecule can achieve gene-specific epigenetic control and provide an approach for the restoration of FMRP in FXS neurons. Full article