Search Results (129,320)

Background: Bacterial keratitis, a major cause of corneal blindness, is frequently associated with biofilm-forming pathogens such as Klebsiella pneumoniae. Cyclic-di-GMP (c-di-GMP) controls biofilm development, which increases antibiotic resistance and makes treatment more difficult, highlighting the need for innovative therapeutic approaches. Methods: This study investigated cinnamaldehyde as a potential ocular therapeutic using combined computational and experimental approaches. Molecular docking and in vitro assays (XTT, resazurin reduction, crystal violet staining, qRT-PCR, and fluorescence microscopy) were used to evaluate the anti-biofilm and immunomodulatory activities of cinnamaldehyde (CA) against Klebsiella pneumoniae. Results: CA inhibited biofilm formation in a dose-dependent manner (≈89% at 1000 µM; >50% at 250 µM), reduced bacterial attachment to contact lenses, and downregulated key biofilm genes (mrkA, mrkC, ybtS, bolA). Docking analysis revealed strong binding affinity to the mrkH regulator (−5.46 kcal/mol. CA maintained more than 80% corneal cell viability by increasing IL-10, suppressing inflammatory mediators (IL-1β, IL-6, and TNF-α), and improving bacterial clearance. Conclusions: This study combines computational docking, biofilm quantification, immune cell assays, and functional gene expression analyses to reveal the ability of cinnamaldehyde not only to suppress biofilm formation but also to enhance macrophage-mediated clearance and modulate corneal immune responses, a multi-target approach not previously described in the context of bacterial keratitis. Such effects highlight its potential as a novel ocular drug candidate for protecting corneal integrity in infectious keratitis. Full article

 Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, continues to be a significant global health issue, especially in Latin America, with increasing international prevalence due to migration. Despite advancements in diagnosis and treatment, it remains a neglected tropical disease characterized by significant morbidity and mortality, mainly influenced by the complex interaction between parasite diversity and host immune responses. Importantly, the remarkable genetic diversity of T. cruzi lineages also contributes to clinical heterogeneity, influencing immune evasion, therapeutic responses, and vaccine feasibility. This review analyzes the impact of immunogenetics on host–parasite interactions in Chagas disease and explores its implications for personalized therapy approaches. Recent research, particularly over the last decade, has indicated that processes including antigenic variation, extracellular vesicle-mediated regulation, and disruption of host signaling pathways facilitate parasite persistence. Host genetic variables significantly influence susceptibility, disease development, and treatment outcomes, including changes in Human Leukocyte Antigen (HLA) genes, cytokine gene polymorphisms, and immunogenetic determinants of cardiac pathology. These findings underscore the potential of immunogenetic markers as tools for prognosis and as targets for personalized therapies. However, there are still considerable research deficiencies. Inadequate comprehension of gene–environment interactions, lack of representation of varied populations, and inconsistencies in study design limit the use of immunogenetic findings in therapeutic settings. At present, the concept of personalized medicine in Chagas disease remains largely aspirational, better understood as a framework for precision public health or stratified interventions guided by host immunogenetic and parasite lineage data. Addressing these issues necessitates comprehensive genomic research, mechanistic investigations of host–parasite interactions, and clinical validation of genetic markers. This study emphasizes the necessity of incorporating immunogenetics into personalized patient management strategies based on existing evidence. This integration has the potential to improve diagnosis, enhance treatment efficacy, and inform preventive interventions, thereby advancing personalized therapy for Chagas disease.  Full article

Background: Atherosclerosis is the pathological basis for lethal cardio-cerebral vascular diseases, such as coronary artery disease and stroke. Fructus Choerospondiatis (FC) has demonstrated cardiac protective effects in multiple ethnomedicine. Whether these protective effects are attributed to the prevention of vascular atherosclerosis, however, remains unknown. We aim to examine the anti-atherosclerotic effect of FC aqueous extract and elucidate the underlying mechanism. Methods: FC was separated into peel and pulp, and the aqueous extract was obtained separately by boiling in water to mimic decocting. Atherosclerosis model was established in ApoE^−/− mice fed with a high-fat diet, and histological analysis were utilized to evaluate the development of atherosclerosis. Various inflammatory models were constructed in mice to evaluate the anti-inflammatory effect of FC extract systemically, including acute local inflammation induced by traumatic injury (ear/foot swelling), acute systemic inflammation triggered by pathogenic infection (LPS- and POLY (I:C)-induced), as well as chronic inflammatory conditions associated with oxidative stress (D-galactose-induced), metabolic disorder (db/db mice), and aging. LC-MS and network pharmacology identified bioactive components and targets. Western blotting, ELISA, qPCR, and immunofluorescence were utilized to analyze the key genes involved in the mechanisms. Results: FC peel extract reduced serum IL-6 level, atherosclerotic plaque area, and macrophage content in the plaque, while pulp extract showed no protective effects. Peel extract exhibits anti-inflammatory effects in all models. The integrative application of LC-MS and network pharmacology identified ellagic acid as the major bioactive component and AKT as its target protein. Mechanistically, FC peel extract inhibits AKT phosphorylation, suppresses c-FOS expression and nuclear translocation, reduces IL-6 transcription and inflammation, and thus alleviates atherosclerosis. Conclusions: FC peel aqueous extract exerts anti-atherosclerotic effect by inhibiting inflammation through AKT/c-FOS/IL-6 axis. This study provides novel insights into the protective effects against atherosclerosis of FC peel and highlights its potential application in the prevention and treatment of coronary artery diseases. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) show durable efficacy in tumors with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), yet clinical responses remain heterogeneous. This study aimed to define immune subgroups within dMMR/MSI-H tumors and develop a reproducible transcriptomic signature predictive of ICI response. Methods: Four MSI-H-enriched cancer types (UCEC, COAD, READ, STAD) from The Cancer Genome Atlas were analyzed. Tumors were stratified by immune cell infiltration (MCP-counter immune composite score) and T-cell-inflamed gene expression profiles (GEP score). Integrating these two axes defined four immune subgroups. Differential expression, random forest feature selection, and pathway enrichment were performed to identify immune programs. A 20-gene immune signature representing the most immune-active subgroup was developed and validated across TCGA, GEO (GSE39582), and IMvigor210 cohorts. Results: Among the four subgroups, the most immune-active group showed strong activation of interferon signaling, antigen presentation, and T-cell-mediated pathways. The 20-gene signature—including CD74, STAT1, TAP1, and HLA-class genes—achieved high reproducibility (mean AUC = 0.95 ± 0.02; accuracy ≈ 89%). In the IMvigor210 cohort, this signature identified tumors with higher PD-L1 blockade response (55.6% vs. 32.8%, p = 0.034) and improved survival trends in the TMB-high subset. Conclusions: The proposed 20-gene signature quantitatively captures immune heterogeneity in dMMR/MSI-H tumors and serves as a practical, interpretable biomarker to identify true ICI responders and guide precision immunotherapy. Full article

Traditional methods for grapevine (Vitis spp.) breeding are marked by lengthy breeding cycles with usually low efficiency, rendering them inadequate for the demands of the rapidly evolving grapevine industry. While grapevine genetic transformation holds significant potential for improvement, its application is hampered by bottlenecks in efficiency, speed, and genotype dependence. In this context, this review systematically examines the factors influencing and challenges associated with key steps in grapevine genetic transformation—specifically, gene delivery and plant regeneration. It posits that the development and application of marker genes, the exploration and utilization of developmental regulators, and the establishment of novel genetic transformation systems are effective strategies to overcome current limitations. In this paper, we present a foundation and methodological guidance for creating efficient and stable genetic transformation systems for grapevine, with significant theoretical and practical implications. Full article

Lupus nephritis (LN) can affect up to 60% of patients with systemic lupus erythematosus (SLE). The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study aimed to evaluate the role of the NLRP3 inflammasome as a predictor of response to immunosuppressive treatment in patients with active LN. A prospective cohort study was conducted with 20 adult patients with active LN, classes III, IV, and V, from January 2021 to September 2023. Patients were followed up at biopsy (T0) and 6 months (T6) and 12 months (T12) after treatment and classified according to the primary efficacy renal response (PERR) at 12 months. Gene expression of NLRP3, CARD8, CASP1, IL1B, and IL18 was evaluated by RT-qPCR in PBMCs. Immunohistochemistry (IHC) for NLRP3 was performed on kidney tissue. The concentration of cytokine IL-1β was measured using the BD™ Cytometric Bead Array (CBA). The mean age was 31.9 ± 8.3 years, with 19 females and 1 male. After 12 months, 65% of patients achieved PERR. The IHC intensity in inflammatory cells was higher in patients with no PERR (p = 0.0426). In the no-PERR group, the gene expression of IL1B showed a significant increase at T6 (FC = 2.22: p = 0.0037) and T12 (FC = 2.91; p = 0.0001) compared with T0. Relative expression of IL1B was higher in no-PERR patients at T12 compared to the PERR group (p = 0.0477). The no-PERR group also had higher serum IL-1β levels compared to the PERR group at 12 months (2.9 ± 0.5 vs. 2.5 ± 0.7, p = 0.0164). In conclusion, our study evidenced an increase in IL1B expression and IL-1β levels over the 12 months of treatment in no-PERR patients, suggesting a potential biomarker of disease activity. Furthermore, a strong NLRP3 IHC staining score was associated with a higher likelihood of no PERR, highlighting the potential of the NLRP3 inflammasome as a predictor of worse clinical outcomes. Full article

Antisense genes (usually suffixed by -AS) represent a class of long non-coding RNAs (lncRNAs) transcribed from the opposite strand of annotated human genes or exon(s). A total of ~2236 human antisense genes exist in the human genome. Their genomic locations with respect to the corresponding sense genes, their dysregulated expression patterns in cancer specimens, and clinical associations with patient outcomes reveal their potential importance in clinical settings. As of today, there lacks a comprehensive review of HNC-associated antisense genes/transcripts to help move forward the antisense field for genetic biomarker development or future drug research. In total, 2.3% (52/2236 antisense genes) of all known human antisense genes have been investigated in head and neck cancer (HNC). Thus, we perform a comprehensive review of the genomic aberrations (mutations, copy number changes, RNA-expression dysregulation, and single nucleotide polymorphisms) associated with HNC patient prognosis, disease progression, cancer cell signaling, drug sensitivity, and radio-resistance. Four antisense genes, namely HOXA10-AS, LEF1-AS1, MSC-AS1, and ZEB2-AS1, have been clinically cross-validated and have consistently demonstrated to be associated with patient outcomes in multiple independent cohorts by different research teams, with clear evidence for the prioritization of clinical biomarker development in HNC. Single nucleotide polymorphisms (SNPs) of antisense genes with evidence for HNC risk or outcomes should be further validated in different ethnic groups, for potential global HNC applications. Full article

The HOX gene family plays an indispensable role in regulating embryonic development, cell differentiation, and morphogenesis. This study employed bioinformatics approaches for systematic analysis, ultimately identifying 33 HOX gene family members from the donkey genome. Physicochemical property analysis revealed that the number of amino acids encoded ranged from 94 to 444, with 31 members classified as alkaline proteins. Their secondary structure was predominantly composed of random coils and alpha helices, and all members were localized to the nucleus. Conserved motif analysis further demonstrated that all donkey HOX family proteins contained highly conserved motifs 1 and 2. Along with three other species, the 33 donkey HOX genes were clustered into eight phylogenetic subgroups. Furthermore, collinearity analysis indicated a high degree of collinearity between the donkey and horse HOX gene families. Gene Ontology analysis confirmed the significant role of the donkey HOX gene family in regulating embryonic development and skeletal system formation. Tissue expression profile analysis revealed significant differences in the expression levels of the 33 HOX genes across 13 different tissues. This study not only systematically identified and characterized the donkey HOX gene family but also provided valuable insights into the genetic regulation mechanisms of key traits in donkey molecular breeding. Full article

The giant freshwater prawn Macrobrachium rosenbergii is a globally farmed decapod species of high economic and nutritional value, but its genetic improvement has been constrained by the lack of an efficient genome editing workflow. Here, we optimized a CRISPR/Cas9 microinjection system for targeted mutagenesis in M. rosenbergii embryos. A controlled mating-based approach enabled routine collection of one-cell embryos, and developmental staging identified 0.5–2 h post-fertilization as the optimal injection window. Optimization of the needle tip (~1 μm) minimized mechanical damage, lowering early embryo mortality to ~10%. Using this system, the eye-development gene MrPAX6 and the sex-related gene MrIAG were successfully edited. MrPAX6 editing produced a 46.9% mutation rate and an average 50% reduction in eye pigment area. MrIAG editing achieved an 84% mutation rate, while post-injection survival to hatching was approximately 35%. These results establish an efficient and reproducible CRISPR/Cas9 editing system in M. rosenbergii, providing a foundation for functional genomics and genetic improvement in this commercially important prawn species. Full article

The integration of artificial intelligence (AI) with medical genetics is transforming healthcare by addressing the analytical challenges posed by the vast complexity of multi-omics data. This review explores the synergistic convergence of these fields, highlighting AI’s transformative role in enhancing diagnostic precision, enabling non-invasive molecular profiling through imaging-genetics, and advancing predictive and personalized medicine via polygenic risk scores and pharmacogenomics. AI is also emerging as a powerful generative tool in therapeutic design, accelerating drug discovery, protein engineering, and precision gene editing. However, this powerful synergy introduces significant ethical, regulatory, and biosecurity challenges, including data privacy, algorithmic bias, and the dual-use risks of AI-enabled genetic engineering. The future envisions a responsible co-evolution, with multimodal AI and the concept of the Digital Twin driving precision medicine, underpinned by interdisciplinary collaboration to ensure fairness, transparency, and societal trust. This article charts the current landscape and proposes actionable directions, emphasizing the need for robust governance to harness AI’s potential while mitigating its risks for the benefit of human health. Full article

Background/Objectives: Capsanthin is a xanthophyll carotenoid from Capsicum species with an extended conjugated polyene chain that underlies both its orange–red color and strong antioxidant potential. In this study, we investigated whether capsanthin protects RA-differentiated SH-SY5Y neuron-like cells against glutamate-induced stress. Methods: Neuronal dysfunction was induced by glutamate exposure, and capsanthin treatment was evaluated using cell viability, reactive oxygen species (ROS) production, antioxidant defense markers, inflammatory cytokines, mitochondrial energy status, and apoptosis-related endpoints. Antioxidant responses were assessed using superoxide dismutase, catalase, glutathione peroxidase activities, and total antioxidant capacity. Cytokine release (TNFα, IL-6, IL-8, IL-4, IL-10) was quantified by ELISA. Mitochondrial function was monitored using ATP content. Apoptosis-associated genes (BAX, BCL-2, CASP3, and CASP9) were analyzed using SYBR Green-based RT-qPCR, complemented by caspase-9 ELISA and caspase-3 Western blotting. Results: Glutamate increased oxidative stress and shifted the cytokine profile toward a pro-inflammatory state, accompanied by reduced ATP levels and a pro-apoptotic transcriptional pattern. Capsanthin significantly attenuated glutamate-induced ROS production, stabilized antioxidant enzyme activities and total antioxidant capacity, reduced pro-inflammatory cytokines while supporting anti-inflammatory signaling, and preserved ATP levels. Conclusions: Overall, capsanthin mitigated excitotoxic stress by maintaining redox balance, limiting inflammatory responses, and protecting mitochondrial energy metabolism in neuron-like cells, supporting its potential as a neuroprotective candidate for glutamate-induced neuronal stress. Full article

Background: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare multisystemic neurodevelopmental disorder caused by pathogenic variants in the Activity-Dependent Neuroprotective Homeobox Protein (ADNP) gene. Since the extensive clinical description of a cohort of 78 affected individuals in 2019, numerous reports described additional cases affected by the condition. However, no systematic synthesis of the clinical and molecular spectrum of these additional individuals has been conducted to date. Methods: In accordance with the PRISMA 2020 guidelines, we performed a systematic review of all publications describing individuals with genetically confirmed HVDAS. Clinical characteristics, comorbidities, and developmental milestones were systematically extracted to illustrate novel or underrecognized manifestations. Results: A total of 105 individuals reported across 34 publications were included. Of these, 66 were clinically and genetically evaluated, and 39 were analyzed only at the genetic level. Our analysis refines the phenotypic spectrum of HVDAS, including developmental delay, visual anomalies, and congenital heart defects. The additional literature also allows us to characterize in more detail the ophthalmological abnormalities, gait disturbances, and the cognitive profile of HVDAS. Advances in ADNP methylation profiling further enhance diagnostic precision and variant interpretation in this evolving neurodevelopmental syndrome. Conclusions: This systematic review provides a comprehensive synthesis of the clinical, genetic, and epigenetic landscape of HVDAS. It underscores the multisystemic nature of the disorder and the need for multidisciplinary management. The expanding phenotypic heterogeneity likely reflects both improved clinical recognition of the more subtle features and the tendency to prioritize publication of more complex or severely affected cases. Full article

Vacuolar H⁺-ATPases play crucial roles in plant ion homeostasis and stress adaptation, yet the functional characterization of their subunit genes in purslane remains limited. In this study, PoVHA-a3, encoding a tonoplast-localized V-ATPase a3 subunit, was identified as a key salt-responsive gene through transcriptomic analysis. Integrated bioinformatic analysis and molecular docking simulations predicted specific binding of NAC3, MYB1, and bHLH62 to the PoVHA-a3 promoter, suggesting their synergistic role in regulating PoVHA-a3 expression. Under salt stress, PoVHA-a3 transgenic Arabidopsis lines exhibited elevated endogenous abscisic acid levels and upregulation of signaling genes (AtNCED3, AtRD29A, AtCOR15A), while the brassinosteroid signaling pathway was suppressed, as indicated by the reduced expression of AtBZR1 and AtEXPA8. Meanwhile, the transgenic lines demonstrated enhanced ATP levels, respiratory rate, and V-ATPase activity. In addition, PoVHA-a3 expression led to greater accumulation of osmoprotectants (proline, soluble sugars and proteins), higher activities of antioxidant enzymes, and reduced levels of oxidative stress indices. Furthermore, a significantly lower shoot Na⁺/K⁺ ratio was observed in transgenic plants, indicating improved ion homeostasis. In conclusion, this study demonstrates that PoVHA-a3 acts as a pivotal positive regulator of salt tolerance in purslane, providing a valuable genetic resource for enhancing salt tolerance in crops through genetic engineering. Full article

Immune checkpoint blockade is one of the current treatments for glioblastoma (GBM), which is still a very aggressive and treatment-resistant tumor of the central nervous system. This study focused on the LYZ gene to find new therapeutic targets. We performed a thorough screening of differential gene expressions between GBM and normal samples using many databases (TCGA, GTEx, GEO, and CGGA). Because LYZ is significantly upregulated in GBM tissues and is associated with shorter patient survival periods, we identified it as a gene of interest. LYZ’s position on the exterior side of the plasma membrane and its participation in leukocyte-mediated immunity were identified by functional enrichment analysis, indicating a role in cell surface immune responses. Significant associations between LYZ expression and particular immune cell types were found using immune infiltration analysis, suggesting that LYZ may have an impact on the tumor microenvironment. Within GBM, single-cell research verified LYZ expression in macrophages and monocytes. LYZ was shown to express differently in GBM cell lines than in normal glial cells, according to cellular experimental verification. The LYZ gene’s functional importance in the pathophysiology of GBM was highlighted by the dramatic reduction in cell proliferation, motility, and invasion that resulted from its knockout. These results suggest that LYZ is a viable therapeutic target and possible GBM diagnostic biomarker, which calls for more research into its mechanisms of action and potential clinical use. Full article

Background: Gene therapy has experienced significant development since its origin decades ago, resulting in therapies for a wide range of diseases. In this context, optogenetics has emerged as a promising therapy for treating diseases in a precise spatiotemporal way using light. Transporting optogenetic genes to target cells is achieved using viral vectors, specifically AAV vectors. These vectors present limited cargo capacity, and a large percentage of the population carries AAV neutralizing antibodies. In this regard, lipid nanoparticles can overcome some of the previously mentioned problems of AAV vectors, making them prime candidates for optogenetic delivery. Methods: In this study, we evaluated their suitability for the delivery of the ChrimsonR plasmid in neurons in vitro. Results: In rat cortical neurons, in most of the concentrations tested, there was no reduction in several neuron morphological parameters that we measured when compared to another non-viral nanoparticle called lipofectamine. Transfection efficiency was significantly higher compared to lipofectamine in almost all treatments. Further in vitro analysis showed that electrophysiological parameters were altered, with reduced signal amplitudes; however, cell viability assays showed no decline in cell viability. Conclusions: These results demonstrate that lipid nanoparticles represent a promising non-viral platform for optogenetic delivery, though formulation optimization is required to achieve full functional efficacy. Full article