Search Results (2,723)

The present study evaluated the effects of the prepartum administration of immunotropic preparations on the growth performance, physiological status, and metabolic profile of calves. Sixty pregnant Holstein cows were divided into three groups (n = 20 each): the first experimental group received a single intramuscular injection of sodium nucleinate (5 mL), the second experimental group received a single intramuscular injection of Ribotan (5 mL), and the control group received saline solution. All treatments were administered 3–9 days before calving. The obtained calves were monitored until 60 days of age. Clinical, growth, hematological, and biochemical parameters were assessed at days 1, 10, 30, and 60. Calves from the treated cows showed improved neonatal adaptation, including faster development of standing posture and the suckling reflex. Body weight was significantly higher in experimental groups at 30 and 60 days (p ≤ 0.05), with consistently greater average daily gains. Blood analysis revealed increased total protein, albumin, and γ-globulin levels, indicating enhanced protein metabolism and immune status. In contrast, cortisol concentrations were lower in treated groups, reflecting reduced physiological stress. Multivariate (PCA) and correlation analyses confirmed strong associations between growth performance, metabolic activity, and immune indicators, and demonstrated clear separation between control and treated groups. Ribotan exhibited the most pronounced biological effect, while sodium nucleinate showed moderate but consistent improvements. In conclusion, prepartum immunotropic treatment of cows enhances early-life adaptation, metabolic efficiency, and growth performance of calves and may represent a practical strategy for improving calf rearing outcomes in dairy farming systems. Full article

Transposable elements (TEs) are inserted into the genome and may change its properties; those occurring in or near regulatory regions may also alter gene expression. Given the challenges of detecting insertions in short-read sequencing, we analyzed structural variants in polar and brown bear genomes by a reciprocal alignment of one species’ sample genomes to a reference sequence of the other species, thus inferring TE insertion as the other genome’s “deletions”. With this approach, we detected short interspersed elements (SINEs) belonging to the CAN SINE family as dominant fixed TEs. We observed a non-random distribution of CAN SINE insertion positions near both protein- and RNA-coding genes, where TEs often overlap UTRs or occur in their vicinity. In contrast, SINEs avoid coding sequences, suggesting TE insertions that would disrupt such sequences are under purifying selection. We used black bear as an outgroup and determined that most of the CAN SINE insertions in the polar bear genome were derived, since they are not present in black or brown bear, while there is no dominant trend for CAN SINE insertions in brown bear relative to the outgroup. Many of the genes with UTRs affected by CAN SINEs are potentially relevant to the differences between the species (body shape, size, etc.) or to Arctic-adaptation phenotypes such as fur color, metabolism, and the immune system. This supports a model that CAN SINEs have contributed to regulatory evolution in bears and provides further evidence of such events across carnivore genomes in the animal kingdom. Full article

Plants must continuously balance the trade-offs between growth and defense, a constraint that is exacerbated by biotic and abiotic stresses, particularly when they occur together. Ethylene (ET) serves as a central, integrative regulatory node controlling this by linking developmental programs to stress-responsive signaling networks. Advances at the molecular and systems levels have revealed that ET mediates the redistribution of metabolic resources via coordinated regulation of its synthesis, perception, and downstream signaling. The ETR (Ethylene Receptor)-CTR1 (Constitutive Triple Response 1)-EIN2 (Ethylene Insensitive 2)-EIN3(Ethylene Insensitive 3) signaling module lies at the core of this network, integrating multiple hormonal pathways. Through dynamic crosstalk with jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), auxin (AUX), and gibberellins (GA), ET enables the fine-tuned coordination of growth inhibition, immune activation, and stress acclimation in response to environmental fluctuations. Processes such as induced systemic resistance, programmed cell death, and architectural plasticity further reinforce this regulatory framework, with ethylene-responsive transcription factors, including ERFs (ethylene responsive factor gene family) and WRKYs, acting as critical convergence points. Emerging insights into ACC (1-aminocyclopropane-1-carboxylic acid) -dependent signaling, chromatin remodeling, and tissue-specific regulation expand the functional scope of ET beyond traditional hormone paradigms. At the same time, the ability of pathogens to manipulate ET signaling underscores its dual role in both promoting immunity and facilitating susceptibility. By integrating molecular, physiological, and ecological perspectives, this review highlights ET as a central coordinator of plant stress resilience and growth optimization, providing a unifying framework for understanding how plants adapt to complex and dynamic environments. Full article

While chimeric antigen receptor (CAR)-T-cell therapies have shown significant effectiveness in hematological malignancies, their efficacy in solid tumors remains limited by the hostile tumor microenvironment (TME) and antigen heterogeneity. Recently, CAR-Macrophage (CAR-M) therapy has emerged as a paradigm-shifting approach, leveraging the innate capability of macrophages to deeply infiltrate tumors and their plasticity to reverse immunosuppression. Unlike T cells, CAR-Ms not only mediate direct phagocytosis but also initiate epitope spreading, effectively bridging innate and adaptive immunity. This review critically examines the trajectory of CAR-M therapy from biological rationale to clinical reality. We dissect the engineering evolution of CAR constructs, arguing for macrophage-specific signaling domains (e.g., FcRγ, Megf10) over traditional T-cell designs. Crucially, we address the major bottlenecks in clinical translation, including the manufacturing challenges of non-expanding primary macrophages and the emerging shift toward induced pluripotent stem cell (iPSC)-derived platforms. Furthermore, we evaluate current clinical trial landscapes and discuss next-generation strategies such as in vivo programming via lipid nanoparticles (LNPs) and synthetic logic-gating to enhance safety. Ultimately, overcoming manufacturing constraints and optimizing delivery systems will be pivotal for CAR-M to evolve from a niche therapy into a standard-of-care modality for solid tumors. Full article

The innate–adaptive immune interface is a decisive control point determining whether therapeutic interventions induce durable protection, antitumor immunity, inflammatory, or immune tolerance. Many immunotherapies fail in translation because immunity is often treated as a single-output system rather than a spatially and temporally organized network shaped by tissue context, antigen-presenting cell fate, biomolecular conditioning, and metabolic state. This review introduces the immunoscape framework as a nanobiotechnology-oriented model for linking immune-state mapping with controllable translational variables, including delivery route, release kinetics, first-contact immune cells, lymphatic routing, biomolecular corona identity, antigen-presenting cell fate, and safety-gate assessment. Unlike systems immunology, which primarily describes immune networks, or conventional immune engineering, which often focuses on selected payloads, targets, or platforms, the immunoscape framework provides a design layer for predicting context-dependent immune outcomes. We discuss two converging strategies for reprogramming this interface: natural biologics, including beta-glucans, polyphenols, microbial metabolites, and extracellular vesicles; and smart nanomaterials, including lipid nanoparticles, biomimetic vesicles, lymph node-targeted platforms, and stimulus-responsive nanoarchitectures. We further propose translational design rules to guide clinically realistic immune-reprogramming nanomedicines for cancer, infectious, inflammatory, and regenerative applications. Full article

Background/Objectives: Immune checkpoints are critical regulatory pathways that maintain peripheral tolerance and prevent autoimmunity. Among these, the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis serves as a major inhibitory pathway that terminates T cell responses. While protein-based checkpoint blockade (ICB) targeting this axis has revolutionized clinical cancer therapy, its clinical efficacy is frequently limited by low response rates, immune-related adverse events (irAEs), and the emergence of adaptive resistance. To break through these bottlenecks, genetic interruption has emerged as a high-precision alternative to modulate the PD-1/PD-L1 pathway at the nucleotide level. Methods: A comprehensive systematic review of literature was performed across major databases (PubMed, Web of Science), with a focus on high quality studies published up to 2026. Results: Direct genomic disruption via CRISPR/Cas9 and post-transcriptional silencing through RNA interference can effectively neutralize inhibitory signaling at its source. Recent advances demonstrate that targeting upstream regulatory nodes—including metabolic checkpoints (e.g., lactate metabolism) and biophysical mechanisms (e.g., liquid–liquid phase separation)—provides superior transcriptional control over PD-L1. Furthermore, engineering CAR-T cells with multiplex gene editing (e.g., TCR/B2M/PD-1 knockout) or localized scFv secretion significantly enhances antitumor potency while reducing systemic toxicity. Innovations in organ-targeted lipid nanoparticles and stimuli-responsive biomimetic carriers further address the delivery barriers in solid tumors. Conclusions: Gene therapy provides a high-precision platform for PD-1/PD-L1 modulation, offering a viable strategy to overcome adaptive resistance. Future clinical application depends on the refinement of safer editing tools, such as base editing, and the standardization of intelligent delivery systems to ensure controllable and scalable cancer immunotherapy. Full article

Background/Objectives: Liposarcoma is a heterogeneous soft tissue sarcoma in which anthracycline-based chemotherapy, including doxorubicin, remains a cornerstone of treatment for advanced disease. However, variable and often limited therapeutic responses highlight the need for improved understanding of disease-associated transcriptional adaptation under chemotherapeutic stress. In this study, a bioinformatics-driven transcriptomic analysis was performed to characterize gene expression alterations associated with doxorubicin treatment in liposarcoma using publicly available data from the Gene Expression Omnibus (GSE12972). Results: Differential expression analysis identified 365 significantly altered genes, including 164 upregulated and 201 downregulated transcripts in treated samples compared with untreated controls. Functional interpretation using Ingenuity Pathway Analysis identified transforming growth factor beta 1 (TGFB1), tumor necrosis factor (TNF), and SMARCA4 as prominent predicted upstream regulators associated with transcriptional programs related to extracellular matrix remodeling, inflammatory and immune modulation, epithelial-to-mesenchymal transition-like states, and chromatin-mediated transcriptional plasticity. Enriched canonical pathways included Liposarcoma tumor microenvironment-associated signaling and fibrosis-related pathways, reflecting stromal activation and immune-related transcriptional changes. Notably, fibroblast growth factor 1 (FGF1) emerged as a supportive regulatory node linked to survival- and anti-apoptotic gene expression patterns. Conclusions: Collectively, these findings provide a disease-oriented, cross-subtype systems-level view of the transcriptional changes associated with doxorubicin treatment in liposarcoma. This work is intended as a hypothesis-generating framework that may inform future functional studies and integrative approaches aimed at understanding therapeutic response and disease progression. Full article

Immune-mediated myocardial injury is an important yet underrecognized manifestation of systemic rheumatic diseases and represents a biologically heterogeneous process extending beyond traditional cardiovascular complications such as pericardial disease or accelerated atherosclerosis. This review aimed to summarize current evidence regarding the molecular mechanisms underlying autoimmune myocardial injury and propose an integrated pathogenic framework. A structured narrative review of the literature was performed, focusing on molecular and cellular mechanisms, disease-specific pathogenic pathways, advances in cardio-immunology, and contemporary diagnostic approaches in autoimmune myocardial disease. Current evidence indicates that myocardial injury in rheumatic diseases results from complex interactions involving autoantibody-mediated injury, immune complex deposition, endothelial dysfunction, coronary microvascular dysfunction, dysregulated innate and adaptive immunity, oxidative stress, mitochondrial dysfunction, immunometabolic reprogramming, and regulated cardiomyocyte death. These mechanisms contribute to heterogeneous clinical manifestations, including myocarditis, arrhythmias, inflammatory cardiomyopathy, and heart failure. An integrated immune–microvascular–immunometabolic framework may represent a central mechanism driving myocardial injury and progression to inflammatory cardiomyopathy, supporting earlier diagnosis, improved risk stratification, and the development of precision therapeutic strategies. Full article

Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive and heterogeneous malignancies worldwide, characterized by high rates of locoregional recurrence, metastatic dissemination, and therapeutic resistance. Angiogenesis plays a central role in tumor progression by supporting vascular remodeling, hypoxia adaptation, invasion, immune evasion, and metastatic spread. In HNSCC, angiogenic activation is regulated through complex interactions involving hypoxia-inducible factors, vascular endothelial growth factor (VEGF) signaling, stromal remodeling, inflammatory pathways, and epigenetic mechanisms within the tumor microenvironment. Recent evidence has also highlighted the role of non-coding RNAs, particularly microRNAs, and exosome-mediated communication in modulating angiogenic and immune-related signaling pathways. Although antiangiogenic therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated biological activity in HNSCC, their clinical efficacy remains limited by tumor heterogeneity, adaptive resistance mechanisms, toxicity, and the lack of validated predictive biomarkers. Several emerging therapeutic strategies are under preclinical or early clinical investigation in HNSCC, including miRNA-based approaches, nanoparticle-assisted delivery systems, vascular normalization concepts, and combinations with immune checkpoint inhibitors; however, robust clinical evidence for most of these strategies remains limited, and their translation to routine practice requires further validation. This review provides a comprehensive overview of the molecular mechanisms regulating angiogenesis in HNSCC and critically discusses current and emerging pharmacological strategies targeting these pathways. Particular emphasis is placed on VEGF/VEGFR signaling, the integration of miRNA and exosome biology, resistance mechanisms, and translational perspectives for biomarker-guided personalized therapy. The novelty of this review lies in the systematic integration of miRNA- and exosome-mediated angiogenic regulation, therapeutic resistance pathways, and precision medicine strategies into a unified pharmacological framework, addressing gaps not fully covered by prior reviews focused primarily on VEGF-targeted agents. Full article

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and reversible depletion of targeted macrophage populations, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablation. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Secreted Phosphoprotein 1 (Spp1) (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which Cx3cl1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation. Full article

During atmospheric reentry, a spacecraft is enveloped by a turbulent plasma sheath that induces severe signal degradation and communication blackout. Conventional mitigation strategies primarily focus on reducing average attenuation but fail to address the dynamic fluctuations in plasma density (typically 20¨C40%), which cause significant group velocity dispersion (GVD), pulse broadening, and intersymbol interference. To overcome this limitation, this paper proposes an active decoupling framework that dynamically tunes an external magnetic field to suppress turbulence-induced signal distortion in the reentry plasma sheath. By establishing a wave propagation model for right-hand circularly polarized (RCP) waves in magnetized collisional plasma and introducing a sensitivity analysis of propagation parameters with respect to plasma density fluctuations, we derive the condition under which the first-order sensitivity of GVD vanishes. Under this condition, a dynamic balance between collisional effects and frequency detuning renders the system immune to density perturbations, effectively decoupling signal transmission from plasma turbulence. Numerical simulations demonstrate that, under optimal parameter matching satisfying the dispersion immunity condition ($\Delta {\omega }_0^2=3{\nu }_e^2$), pulse broadening can be suppressed by several orders of magnitude, and the broadening factor remains near unity over extended propagation distances. It is further shown that this optimal condition is highly sensitive to plasma parameter evolution, motivating the necessity of adaptive magnetic field control in dynamically evolving reentry environments. This work provides a novel physical-layer paradigm for mitigating reentry blackout by actively decoupling signals from turbulence via dynamically tuned magnetic fields. Full article

Background: Prolonged intermittent fasting is associated with metabolic and immune adaptation; however, the extent to which transcriptional immune responses translate into systemic inflammatory changes, and how these processes relate to autophagy, senescence-associated signaling, and inflammasome regulation, remains incompletely understood. Methods: This study represents a secondary integrative analysis of a previously characterized cohort of healthy young men undergoing Ramadan fasting. Longitudinal data across four time points (T1–T4) were re-analyzed, integrating targeted mRNA profiling of autophagy-, senescence-, and inflammasome-related genes with circulating cytokines and clinical parameters. Baseline-stratified regression and exploratory clustering were applied to assess inter-individual variability. Results: Fasting was associated with modest reductions in body weight (−1.78 ± 1.44 kg, FDR < 0.001) and BMI (−0.56 ± 0.47 kg/m², FDR < 0.001), without hemodynamic instability. Autophagy-related transcripts (ULK1, ATG5) were upregulated, while senescence markers showed divergent regulation (p53↑, p21↓). Inflammasome-related genes (NLRP3, IL1B) increased at the transcriptional level; however, circulating IL-1β and IL-6 remained stable and TNFα decreased (FDR < 0.001), indicating dissociation between transcriptional priming and systemic cytokine output. ΔNLRP3 was inversely associated with baseline expression (β = −1.88, R² = 0.31, p = 0.0056), suggesting baseline-dependent transcriptional responsiveness. Responses followed a continuous spectrum rather than discrete subtypes. Conclusions: Prolonged intermittent fasting is associated with coordinated immunometabolic remodeling characterized by transcriptional changes in autophagy-, senescence-, and inflammasome-related pathways, without systemic inflammatory escalation. Inflammasome-related responses appear baseline-dependent, suggesting graded immunological responsiveness rather than a uniform activation. These findings are hypothesis-generating and support the interpretation of fasting as a graded immunometabolic modulator rather than a uniform pro-inflammatory stimulus within the limitations of a secondary exploratory analysis. Full article

The complement system is a key link between innate and adaptive immunity, contributing to pathogen elimination, immune regulation, and tissue homeostasis. Its activation is not only crucial in infections, such as COVID-19, but also plays a major role in the pathomechanism of several non-infectious respiratory diseases, such as asthma, COPD, sarcoidosis and lung cancer. Complement components can modulate the quality of the adaptive immune responses, including through the regulation of T2 immunity and eosinophilic inflammation, thereby linking natural defense to complex immune processes. In recent years, it has become increasingly clear that dysregulated complement activity contributes to inflammation, thrombosis and tissue damage in a wide range of respiratory diseases. The study of the various components of this cascade system may therefore be promising from both a diagnostic and therapeutic point of view. Some of its components may serve as biomarkers for distinguishing between different phenotypes of certain lung diseases, while their targeted inhibition or modulation may open the way towards new treatment options. A better understanding of the complement system’s integrative and regulatory role not only allows for a deeper insight into immunological interactions but may also bring us closer to phenotype-oriented, immunology-based pulmonology, which may have real clinical benefits in the future. Full article

Prostate disease diagnostics increasingly integrate PSA-derived parameters, molecular assays, risk calculators, and multiparametric MRI, yet important limitations remain in distinguishing benign inflammatory changes from clinically significant prostate cancer and in capturing biological heterogeneity. This narrative review summarizes current evidence on inflammatory and epigenetic biomarkers in prostate disease, focusing on YKL-40, mannose-binding lectin, and global DNA methylation/hydroxymethylation. The reviewed evidence indicates that chronic inflammation, innate immune variability, tumor microenvironment remodeling, and epigenetic dysregulation contribute to prostate disease progression and may provide biological information not fully reflected by conventional diagnostic tools. YKL-40 may reflect inflammatory stromal remodeling and angiogenic activity, mannose-binding lectin may represent innate immune variability, while DNA methylation and hydroxymethylation may indicate systemic molecular adaptation and long-term inflammatory imprinting. However, these biomarkers remain largely investigational and should currently be considered adjunctive biological layers rather than validated standalone diagnostic tools. Future studies should prioritize analytical standardization, prospective prostate-specific validation, and assessment of incremental clinical utility beyond PSA, molecular assays, and mpMRI within clearly defined contexts of use. Full article

The escalating global threat of antimicrobial resistance (AMR) has intensified efforts to identify safe, effective, and sustainable alternatives to in-feed antibiotics in livestock production. The bovine gastrointestinal microbiome plays a central role in host immunity, nutrient utilization, and disease resilience, positioning microbiome-modulating interventions as promising candidates for antimicrobial stewardship. Despite growing experimental interest, a systematic synthesis of the available evidence in cattle is lacking. This systematic review aimed to evaluate the efficacy of microbiome-modulating interventions, including probiotics, prebiotics, postbiotics, phytogenic feed additives, essential oils, organic acids, and native rumen microbial supplements, as strategies to reduce antimicrobial use in cattle, and to characterize their effects on gut microbial diversity, fermentation characteristics, and host health and performance outcomes. A systematic search of Scopus, Web of Science, and EBSCOhost (including Academic Search Ultimate, MEDLINE with full text, and CAB Abstracts with Full text) was conducted in accordance with PRISMA guidelines. Studies were eligible if they used cattle (dairy cattle, beef cattle, calves, or mixed production systems), employed a microbiome-modulating intervention, and reported at least one microbiological or host outcome. Seventeen peer-reviewed studies published between 2010 and 2025 were included after full-text screening. Risk of bias was assessed using an adapted SYRCLE tool, which identified moderate overall study quality; the majority of included studies were randomized controlled trials or controlled experiments, though reporting of allocation concealment and blinding was inconsistent across studies. Across the 17 included studies, five broad categories of interventions were evaluated: probiotics (n = 5 studies), prebiotics (n = 2), postbiotics and organic acids (n = 4), phytogenic additives and essential oils (n = 4), and native rumen microbial supplements (n = 2). Animals spanned neonatal dairy calves, weaned Holstein calves, dairy heifers, lactating dairy cows, and Bos indicus feedlot beef cattle. Probiotics and organic acids most consistently improved growth performance: benzoic acid supplementation increased average daily gain by 8.4% (p < 0.05) and fructo-oligosaccharide prebiotics elevated body weight at weaning by 6.7% (p < 0.01). Native rumen microbial supplements improved energy-corrected milk yield by up to 3.1% without increasing dry matter intake. Polyphenols and bile acids demonstrated the strongest immunological and disease-preventive effects, reducing calf mortality by approximately 40% and disease severity by approximately 35%, respectively. Microbiome analyses revealed intervention-dependent increases in microbial diversity and shifts toward taxa associated with improved fermentation efficiency, including enrichment of propionate-producing Prevotellaceae, butyrate-associated Ruminococcus, and hindgut Bifidobacterium. Rumen fermentation outcomes included reductions in the acetate:propionate ratio and ammonia-N concentrations and improvements in fiber digestibility of 3.6–4.4 percentage units in dairy cows. Phytogenic additives preserved microbial diversity without inducing broad-spectrum suppression, functioning primarily as microbiome stabilizers rather than direct antimicrobial replacements. This systematic review provides evidence that gut microbiome modulation may enhance growth performance, improve fermentation efficiency, and reduce disease susceptibility in cattle, thereby supporting antimicrobial use reduction across dairy, beef, and mixed production systems. Effect magnitudes varied substantially across intervention categories and production contexts, and study quality was moderate, underscoring the need for larger, pre-registered trials with standardized outcome reporting and direct antibiotic comparator arms. Probiotics, prebiotics, and bile acid metabolites showed the greatest potential as components of integrated antimicrobial stewardship strategies in cattle production. Full article