Search Results (5,999)

The Mediterranean mussel, Mytilus galloprovincialis, is currently facing unprecedented mass mortality events (MMEs) that threaten the economic and ecological stability of Mediterranean aquaculture. The present review gathered and analyzed current knowledge on climate change and environmental disorders that may cause MMEs in Mediterranean mussels, compromising mussel physiology and immune competence. Biological agents, which proliferate under stress conditions, can either trigger direct disease or act as co-factors in mortality. The impact of the economic loss following MMEs in mussel production in the Mediterranean Sea is also described. The main key drivers used in the analysis of the literature were “M. galloprovincialis”, “MMEs”, “environmental stressors”, “climate change”, “pathogens”, “pollutants”, “economical losses”. The One Health–One Welfare framework recognizes the inextricable interconnection between the health of human, mussel, and marine ecosystems. This approach is essential for developing holistic monitoring programs, robust risk assessment strategies, and adaptive management policies capable of ensuring the long-term sustainability of Mediterranean mussel production and the ecological stability of coastal systems. In the future, the development of integrated water monitoring systems where mussels are both farmed species and active biological sentinels is possible. The implementation of a digital monitoring system will offer a transformative strategy for mitigating MMEs in Mediterranean mussel populations. Full article

Neoadjuvant strategies in head and neck squamous cell carcinoma (HNSCC) are reshaping therapeutic paradigms by shifting emphasis from anatomical staging toward biology-driven response stratification. The transition from induction chemotherapy to immune checkpoint–based and combination regimens has transformed the perioperative setting into a translational platform that enables interrogation of tumor–immune interactions and clonal selection under therapeutic pressure prior to surgery. In this context, pathological response assessment has emerged as a robust surrogate endpoint, overcoming the limitations of radiologic evaluation, which often fails to capture immune-mediated pseudoprogression and spatially heterogeneous regression. Quantification of residual viable tumor (RVT) provides a reproducible metric of therapeutic efficacy, while characterization of immune-related regression beds, tertiary lymphoid structures, macrophage polarization states, and compartment-specific nodal responses offers mechanistic insight into tumor clearance and resistance evolution. Evidence from phase II trials, single-cell sequencing, spatial transcriptomics, and multiplex immune profiling supports the prognostic relevance of pathology-driven endpoints. Integration of digital pathology and artificial intelligence–assisted image analysis further enhances reproducibility and enables high-resolution mapping of residual disease and immune architecture. Within this modern oncologic framework, the neoadjuvant-treated specimen functions as a dynamic biomarker platform guiding response-adapted surgical strategies and biomarker-driven clinical trial design. This study was designed as a narrative review. A structured literature search was performed using PubMed and major oncology journals to identify relevant studies on pathology-driven response assessment in neoadjuvant-treated head and neck squamous cell carcinoma. The review focused on publications addressing histopathological response criteria, immune microenvironment remodeling, spatial profiling technologies, and computational pathology approaches. Full article

The mixed lymphocyte reaction (MLR) is a classic functional assay that models in vitro interactions between responder T cells and allogeneic antigen-presenting cells (APCs). It quantifies the magnitude and quality of alloreactivity, integrating signals from allorecognition, co-stimulation, inflammatory context, and minor histocompatibility antigens that may not be captured by molecular matching alone. This review is narrative in nature and is intended as a practical, non-systematic synthesis of the field. To provide a modern, practice-oriented synthesis of MLR designs, readouts, and translational uses, highlighting how new technologies have expanded MLR from bulk proliferation into multidimensional immune profiling.We summarize why MLR remains valuable as a functional compatibility probe beyond HLA typing, including the high baseline frequency of alloreactive T cells that produces robust signals without priming. We then review key design options (one-way vs. two-way formats; stimulator inactivation; responder definition; APC source and maturation) and how these choices affect interpretation for rejection and graft-versus-host disease risk modeling, tolerance-focused studies, and immunomodulatory screening. Next, we outline major readouts—radiometric and flow cytometric proliferation (dye dilution, Ki-67), cytokine/chemokine profiling, cytotoxicity adaptations, and next-generation add-ons (e.g., scRNA-seq, TCR sequencing)—emphasizing complementary strengths and common pitfalls. Finally, we consolidate practical quality and reproducibility controls (donor variability, dynamic range, timing, batch effects, and acceptance criteria) to improve cross-study comparability and translational readiness. Modern MLR platforms combine controllable allogeneic stimulation with scalable, high-resolution readouts for mechanistic discovery, immune monitoring and translational immune profiling. Standardized modular design and rigorous quality control can improve reproducibility and support broader adoption across transplantation, immunotherapy, and immune-modulation research. Full article

Glioblastoma (GBM) persists as one of the greatest challenges in the treatment of human cancer, despite extensive efforts to leverage the therapeutic potential of immunotherapy. While checkpoint blockade and other forms of immunotherapy have revolutionized the treatment of various cancers, their therapeutic efficacy in GBM has been hindered by the profound immunosuppressive environment, spatial heterogeneity, and dynamic immune metabolic challenges associated with the tumor microenvironment. In this review, we will synthesize recent advances and insights to develop a next-generation framework for GBM immunotherapy based on systems biology approaches to understanding the complex interplay between GBM and the immune system, as opposed to single-axis approaches to immune activation and modulation. We will discuss how the functional competence of the interferon system, myeloid antigen presentation status, T-cell clone status, spatial organization of the immune microenvironment, and resource competition between GBM and the immune system dictate therapeutic responsiveness. Furthermore, the current paper elucidates how recent advances in spatial transcriptomics, single-cell analysis, and high-parameter imaging enable us to understand how immune phenotype status varies across GBM regions and treatment status, and how this information can be used to develop predictive and pharmacodynamic biomarkers of therapeutic efficacy and failure. We will then discuss how these advances form the basis for rational combination approaches to GBM immunotherapy, which involve the integration of checkpoint blockade with metabolic reprogramming, myeloid modulation, and interferon system reactivation, and how artificial intelligence-based analytics and adaptive clinical trial design can guide the development of biomarker-based therapeutic selection approaches. Full article

Lipids are the major energy reservoir, but excessive fat accumulation drives immune cell trapping, chronic inflammation, autoimmunity, and cancer. Lipid synthesis, secretion, degradation, and the shuttling to cellular organelles and compartments are still poorly investigated in all cell types of the mammalian body. The major routes of FA uptake are dietary uptake, lipolysis, and de novo synthesis. We highlight disease associations zooming in on the Signal Transducer and Activator of Transcription 1/3/5 (STAT1/3/5) molecules in association with cytokine, growth factors, and hormone action, steering lipid metabolism. We compare STAT-lipid crosstalk from nuclear and mitochondrial perspectives, highlighting roles in immunity, metabolic diseases, and cancer, and providing insights into key regulatory mechanisms of lipid metabolism. A high degree of cellular flexibility in metabolic adaptation explains the need for fine-tuning, in which STAT molecules can function as rheostats to maintain energy equilibrium within cellular compartments. This concept bridges, e.g., high-energy flux or the Warburg effect, with the Hydride Transfer Complex upon low-energy provision. Another interesting STAT1/3/5 aspect is their Lipid droplet (LD) association and LD formation. LDs play key roles in disease initiation or progression, including autoimmunity or cancer, as well as chronic inflammatory diseases due to their role in (1) lipotoxicity, (2) cell death regulation, (3) immune system amelioration, and (4) energy provision. Finally, the therapeutic consequences of the angles are outlined, along with future research directions. Full article

Surgical resection remains a cornerstone in the multidisciplinary management of central nervous system (CNS) tumors, particularly diffuse gliomas. Traditionally, the role of surgery has been evaluated primarily through quantitative metrics such as extent of resection and its association with survival outcomes. However, despite maximal and radiologically complete resections, recurrence remains nearly universal in malignant CNS tumors, suggesting that surgical cytoreduction alone does not fully account for post-surgical disease dynamics. Emerging biological and molecular evidence indicates that surgery represents not merely a technical intervention, but a biologically active event that profoundly reshapes tumor evolution and treatment response. In this review, we propose a conceptual framework that redefines surgery as a key biological driver in CNS tumor progression. We synthesize evidence demonstrating that surgical trauma induces inflammation, hypoxia, vascular remodeling, immune modulation, and extracellular matrix reorganization, collectively reprogramming the residual tumor microenvironment. These changes create selective pressures that favor the survival and expansion of adaptive tumor cell subpopulations, including invasive and stem-like phenotypes. From an evolutionary perspective, surgical resection functions as an acute selective bottleneck acting on heterogeneous tumor ecosystems, contributing to clonal selection and molecular divergence at recurrence. We further examine the dissociation between surgical (anatomical) margins and molecular (biological) margins, highlighting how biologically active tumor cells infiltrate beyond radiologically defined boundaries. This discrepancy provides a biological explanation for marginal and distant recurrences and challenges anatomy-based paradigms of surgical completeness. Importantly, we discuss how surgery-induced biological changes influence postoperative radiotherapy and systemic therapies, affecting radiosensitivity, target delineation, and therapeutic vulnerability. Finally, we outline future directions toward surgery-integrated precision neuro-oncology, emphasizing the potential of spatial profiling, liquid biopsy, advanced imaging, and artificial intelligence to capture perioperative tumor evolution. By reframing surgery as a biological inflection point rather than a neutral prelude to adjuvant treatment, this review advocates for a dynamic, biology-driven continuum of care aimed at anticipating tumor adaptation and improving long-term disease control in CNS tumors. Full article

Apostichopus japonicus undergoes evisceration in response to adverse environmental stimuli, and its coelomocytes undergo rapid regeneration within 6–24 h to restore innate immune function. FOS, an immediate early gene, regulates cell proliferation and cycle, but its role in A. japonicus coelomocyte regeneration after evisceration is unclear. In this study, AjFOSL from A. japonicus was cloned, which harbors a 609 bp open reading frame (ORF) encoding 202 amino acids (aa) with a conserved bZIP domain and is localized on chromosome 14. It shares 58% homology with FOS from Holothuria leucospilota and Lytechinus pictus. Phylogenetic analysis revealed that AjFOSL clusters closely with FOS from Magallana gigas and Mytilus edulis. Tissue distribution analysis showed that AjFOSL was widely expressed in various tissues, with the highest expression level detected in the tentacles. Temporal expression profiling demonstrated that AjFOSL was significantly upregulated by 1.75-fold at 6 h after evisceration. After AjFOSL knockdown, the peak expression of Cyclin A, Cyclin B, and E2F was delayed and the coelomocyte number was consistently reduced compared with that in the evisceration-only group. The AjFOSL acted as an immediate early response gene and was associated with the regulation of coelomocyte regeneration by modulating the expression of cell cycle-related genes. This study provides novel insights into the molecular associations underlying coelomocyte regeneration and the evolutionary adaptation of FOS genes in echinoderms. Full article

Next-generation sequencing (NGS) has impacted the treatment landscape for mCRC, leading to improved outcomes through the use of molecularly targeted and immune checkpoint inhibitor therapies. The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) recommend, at a minimum, initial testing to assess RAS, BRAF, HER2, and microsatellite instability (MSI)/mismatch repair (MMR) status, as these results determine therapeutic eligibility. Broader testing to identify the eligibility for tumor-agnostic therapy for a tumor mutation burden (TMB), NTRK gene fusions, and RET fusions is encouraged for all patients with advanced solid tumors. Patients with metastatic disease may develop progressive disease, often as a result of adaptive resistance mechanisms and selective therapeutic pressure on disease heterogeneity. Repeat biomarker testing at progression has the potential to define these resistance mechanisms and to guide the next therapy or clinical trial enrollment. While these practices have become more commonplace, unified guidelines have yet to be established. In this review of the literature, we evaluate the advantages and pitfalls of sequential biomarker testing during disease progression in patients with mCRC. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by aggressive tumor biology, extensive intratumoral heterogeneity, and profound resistance to standard therapies. While recurrent genetic alterations such as KRAS mutations are central to PDAC initiation, growing evidence demonstrates that epigenetic dysregulation is a critical determinant of disease progression, cellular plasticity, immune evasion, and therapeutic failure. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, shape transcriptional programs without altering the underlying DNA sequence, rendering them dynamic and potentially reversible therapeutic targets. This review provides a comprehensive overview of key epigenetic proteins implicated in PDAC, encompassing writers, readers, and erasers of chromatin marks. Aberrant activity of histone methyltransferases and acetyltransferases, bromodomain-containing proteins, histone deacetylases, and demethylases orchestrates transcriptional reprogramming that promotes epithelial–mesenchymal transition, stem-like phenotypes, metabolic adaptation, and resistance to chemotherapy and radiotherapy. In parallel, epigenetic alterations within the tumor microenvironment contribute to stromal activation and immune suppression, further limiting therapeutic efficacy. We summarize recent advances in pharmacological targeting of epigenetic regulators and discuss the rationale for combination strategies integrating epigenetic inhibitors with cytotoxic agents, targeted therapies, and immunotherapies. Emphasis is placed on emerging experimental platforms—including patient-derived organoids, co-culture systems, and in vivo models—combined with multi-omic profiling and computational approaches to identify biomarkers of response and optimize therapeutic design. Collectively, this review highlights epigenetic regulation as a central and actionable vulnerability in PDAC and outlines future directions toward biomarker-guided, personalized epigenetic therapies aimed at overcoming resistance and improving clinical outcomes. Full article

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system (CNS). By acting on the immune system, disease-modifying therapies (DMTs) can control disease activity, but they indirectly increase susceptibility to infections, so different vaccines are necessary to prevent it. DMTs may potentially affect vaccine-induced seroconversion. We aim to analyse the response to the hepatitis B virus (HBV) vaccine (Engerix-B) in relapsing–remitting MS patients (RRMS) using these therapies because the scientific literature remains limited in this area. A retrospective observational study of RRMS patients vaccinated against HBV was conducted. Acquired immunity after vaccination was determined, and an analysis of immunogenicity was conducted based on the type of DMT (immunomodulators/immunosuppressants), vaccine doses, total lymphocyte count (TLC), age, and sex. 200 patients were included, with a mean age 47.79 years, and 140 (70%) were women. A lower vaccine response was observed in patients treated with immunosuppressive DMTs (51.8%, p < 0.001), particularly with fingolimod (32.4%, p < 0.001), and a higher response was seen with immunomodulators like teriflunomide and interferon-β1a (100%, p < 0.001). Using logistic regression, a model was obtained that included the number of vaccine cycles, lymphopenia and type of DMT associated with the response to the HBV vaccine. It is necessary to adapt HBV vaccination protocols for MS patients, considering the type of DMT used and baseline immune status. Full article

The tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), poses a significant threat to global tomato production. However, environmentally sustainable management strategies for this pest, as well as its mechanisms of insecticide resistance, remain insufficiently understood. Broflanilide, a novel meta-diamide compound, can bind specifically to the transmembrane domain of the RDL subunit, causing prolonged opening of the chloride channel, disruption of neurotransmission, and ultimately insect paralysis and death. This study employed the leaf immersion method to conduct bioassays on the second-instar larvae of T. absoluta to evaluate physiological responses to sublethal concentrations of the novel amide insecticide broflanilide. Subsequently, high-throughput transcriptome sequencing was performed to investigate changes in gene expression and metabolic pathways. Bioassay results determined the larval sublethal concentrations of broflanilide to be 0.136 mg/L (LC₁₀) and 0.210 mg/L (LC₃₀). Sublethal exposure significantly prolonged the larval period, reduced pupal weight, and inhibited fecundity of female adults. Transcriptomic and qPCR analyses revealed that, compared with the control (CK), expression of the vitellogenin gene Vg decreased by 15.99% and 30.27% under LC₁₀ and LC₃₀ treatments, respectively, while its receptor gene VgR decreased by 11.56% and 24.49%. Similarly, expression of chitin synthase genes chs1 and chs2 declined by 13.56% and 30.17% (chs1), and 7.85% and 19.45% (chs2), respectively. Gene expression analysis elucidated how sublethal insecticides treatment impact larval development and fecundity. Furthermore, the study revealed upregulation of cytochrome P450-mediated detoxification pathways and Toll/Imd immune signaling pathways under broflanilide stress, indicating activation of a coordinated defense response in T. absoluta. Sublethal broflanilide exposure modulated larval gene expression to balance growth, development, and stress adaptation. Such exposure exerts selective pressure on susceptible populations, potentially driving adaptive shifts in detoxification metabolism and contributing to the development of field resistance. These findings advance our understanding of the sublethal effects of novel insecticides and provide valuable insights for insecticide deployment strategies and resistance management. Full article

The dynamic interaction between plants and their root-associated microbiota represents a sophisticated and profound biological communication that regulates plant development and the formation of adaptation to the surrounding environment. These interactions function as critical regulators of multiple physiological processes, finally influencing soil fertility and agricultural productivity. Plants have evolved epigenetic networks that regulate beneficial plant–microbe interactions through regulating immune responses, gene regulation, and metabolite production to enhance stress tolerance and soil adaptation. These regulations collectively govern microbial colonization patterns while establishing reciprocal feedback loops through root exudate–microbe interactions. This review systematically updates contemporary advances in understanding how epigenetic modifications shape rhizosphere microbiome composition and function, and discusses their potential applications in enhancing the yield and quality of horticultural crops, as well as in mitigating continuous cropping obstacles. Full article

The transition period in dairy cows is marked by metabolic, oxidative, and immune challenges that increase susceptibility to periparturient diseases. Injectable mineral supplementation (IMS) has been proposed to support immunometabolic adaptation by enhancing antioxidant capacity and immune function, with consistent associations with improved health outcomes but variable effects on production. Therefore, this study evaluated the effects of repeated intramuscular multi-mineral supplementation during the transition period on health, metabolic stress, immune status, and productive performance in Holstein cows. Supplementation was associated with lower odds of subclinical hypocalcemia on day 4 postpartum in primiparous cows (p = 0.02) and overall for persistent subclinical hypocalcemia (p = 0.03). Multiparous cows (p = 0.04) and the overall population (p = 0.01) showed consistent effects on metritis following IMS. Supplemented cows had improved metabolic and uterine health indicators without affecting energy metabolism-related disorders. Although no differences were detected for major postpartum health disorders, its main benefits may involve immune competence, oxidative regulation, and physiological resilience rather than energy balance. Full article

Newborn sheep rely on passive transfer of immunity via colostrum as well as innate immunity for survival and adaptation to the extrauterine environment. This study examined associations between immunomodulatory constituents of colostrum, namely, immunoglobulin G (IgG), acute-phase proteins (APPs; serum amyloid A (SAA), and haptoglobin) and interleukin-6 (IL-6), and their corresponding concentrations in serum of 2–3-day-old offspring in a cohort of 296 Dorper lambs across three consecutive years. It also assessed the effects of these immunological markers on average daily weight gain (ADWG) during the first four months of life. IgG, APP, and IL-6 concentrations were measured, and mixed linear regression models were used for all analyses. Colostrum and serum concentrations of IgG and IL-6 were positively associated, whereas SAA levels in colostrum were negatively associated with IgG concentrations in serum. Serum IL-6 concentration was negatively associated with colostrum concentrations of IgG and SAA. Serum IgG concentration was positively associated with ADWG, while SAA and IL-6 concentrations were negatively associated with ADWG. These results show the importance of immunomodulating factors in colostrum other than IgG and emphasize the long-term effect of the serum concentrations of these factors on growth performance. Full article

Human Immunodeficiency Virus Type 1 (HIV-1), the causative agent of the acquired immune deficiency syndrome (AIDS), originated from zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting African great apes, following complex cross-species transmission events and virus–host co-evolution. These processes were accompanied by multiple viral adaptations, particularly within structural and accessory genes, enabling evasion of host restriction factors and long-term viral persistence. In 1988, an antisense open reading frame (ORF) overlapping the env gene was proposed and subsequently confirmed by the identification of antisense transcripts and the antisense protein (ASP). An “intact” ASP ORF (defined as >150 codons) is predominantly conserved in pandemic HIV-1 group M viruses and shows evidence of positive selection, suggesting a selective advantage. Increasing evidence supports the hypothesis that the asp gene emerged de novo during the evolution of group M and contributed to viral adaptation and global spread in humans. This review combines a narrative review of the literature with original in silico analyses of HIV-1 and SIV sequences retrieved from the Los Alamos National Laboratory database. We systematically reassessed the distribution, length variability and conservation of the ASP ORF across HIV-1 groups (M, N, O, P), subtypes, circulating recombinant forms (CRFs), unique recombinant forms (URFs) and related SIV lineages. Our updated analyses confirmed the strong association between the presence of an “intact” ASP ORF and pandemic HIV-1 group M lineages, while revealing rare but notable antisense ORFs in selected SIVcpz and SIVgor strains. By integrating evolutionary, epidemiological and sequence-based evidence, we aim to clarify the origin and maintenance of the ASP ORF and to contextualize its emergence within the broader framework of overlapping gene evolution, de novo gene birth and the selective pressures shaping viral fitness and pandemic potential. Full article