Search Results (1,331)

Echinometra lucunter, the most abundant sea urchin in Brazil, causes numerous accidents by puncture wounds, primarily on hands and feet. Beyond mechanical trauma, recent research has identified bioactive molecules in spine extracts and coelomic fluid contributing to these inflammatory reactions. This study investigated spine morphology to better understand the envenomation and defense processes for the animal. Using various microscopy techniques, the spines were revealed to be mineral structures with longitudinal canals and a sponge-like central mesh rich in granular cells. These cells extend from the spine’s center to its edges, terminating in fimbriae-like structures, likely involved in molecular exchange with the environment. The spine tip is more cellular than the base, suggesting a defensive role, while the base provides structural support. Several cell types were identified, including granulocytes, red spherulocytes, and phagocytic amoebocytes, also found in the coelomic fluid. Other cells displayed prominent Golgi apparatuses and secretory granules, indicating specialized secretory functions, likely the source of bioactive molecules involved in chemical defense and spine regeneration. Understanding this cellular structure is crucial for comprehending the urchin’s envenomation and defense mechanisms. Full article

This study aimed to characterize and evaluate the fibrinolytic, thrombolytic, hematological, and toxicological aspects of a serine protease (AsKSP) from Aspergillus tamarii Kita UCP 1279. The enzyme was purified using a two-phase aqueous system and assessed for optimal pH (7.0) and temperature (50 °C), stability, and effects of metal ions, inhibitors, and surfactants. AsKSP exhibited stability for up to 120 min at 50 °C and 36 h at pH 7.0. Enzymatic activity was enhanced by Na⁺ and Zn²⁺ and non-ionic surfactants (Tween-80) but inhibited by Cu²⁺, Fe³⁺, Triton X-100, and SDS, reducing activity by up to 62.35%. The highest amidolytic activity was observed for the substrate N-succinyl-Gly–Gly–Phe-p-nitroanilide. SDS-PAGE analysis indicated an approximate molecular mass of 90 kDa. The enzyme showed fibrinolytic activity, degrading 38.81% of fibrin clots in vitro after 90 min, without affecting fibrinogen. Cytotoxicity assays indicated no toxicity (cell viability > 80%). Coagulation assays showed slight prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), with no effect on thrombin time. No red blood cell lysis was observed, and albumin increased enzymatic activity by 31.70%. These findings demonstrate that Aspergillus tamarii Kita UCP 1279 produces a fibrinolytic protease with potential for thrombus treatment, providing a promising foundation for drug development. Full article

Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. Full article

Antimicrobial peptides (AMPs) have emerged as promising candidates in the fight against multidrug-resistant pathogens due to their broad-spectrum antimicrobial activity and low potential for resistance development. However, their clinical application is limited by poor stability and susceptibility to enzymatic degradation. This study aims to address these limitations by synthesizing a series of cyclic hexapeptides using the hydrazide method and evaluating their antimicrobial activity and stability. The hydrazide method facilitated the synthesis of 11 cyclic peptides through a reaction between C-terminal hydrazides and cysteine-containing peptides. Antimicrobial assays showed that Cy-f2 and Cy-f4 exhibited potent inhibitory effects against different kinds of bacteria, including E. coli, Staphylococcus aureus, and S. aureus. Hemolysis assays revealed minimal red blood cell lysis at effective antimicrobial concentrations, indicating good biocompatibility. Stability tests demonstrated improved stability of the cyclic peptides compared to linear counterparts in SGF and 80 °C. In conclusion, the cyclic hexapeptides synthesized in this study demonstrate excellent antimicrobial activity, enhanced stability, and low toxicity, suggesting their potential as new candidates for treating drug-resistant bacterial infections. Full article

Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization. Methods: WT and Nrf2-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli. Results: Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation. Conclusions: These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization. Full article

Betalains are hydrophilic natural pigments commonly found in plants of the Caryophyllales order, as well as in specific species and genera of fungi, such as Hygrocybe, Hygrophorus, and Amanita muscaria. Betalains are sorted into two groups: betacyanins, which form red-violet pigments, and betaxanthins, which form yellow-orange pigments. These compounds can be employed as colorimetric sensors and biosensors. This paper provides a review of the isolation methods of betalains and the various applications of betalains as colorimetric sensors and biosensors. The review was conducted by collecting publications over the last decade. The results show that betalains can be used as a colorimetric sensor to identify metal compounds in water and nonmetal compounds that indicate the quality of food. In addition, betaxanthin has been used for developing cell-based biosensors from yeast and bacteria. Furthermore, betalain as a colorimetric sensor and biosensor is developed by using an innovative digital detector, such as a smartphone. Nevertheless, the fragile stability of betalains presents a significant barrier during the extraction. As a result, future studies could focus on adding innovative technologies for optimizing extraction and also developing betalain as novel bio-indicators for specific analytes. Full article

Athletes engaged in dynamic sports experience a shortened red blood cell (RBC) lifespan and accelerated turnover due to RBC destruction. This accelerated RBC turnover might have a positive impact on exercise performance by increasing the number of young red blood cells with a high oxygen-carrying capacity. However, accelerated turnover might also be a result of intravascular haemolysis caused by RBC destruction during exercise, impairing RBC function and oxygen transport. Therefore, we aimed to evaluate the relationship between reticulocyte count as an indicator of short-term RBC profile changes and exercise capacity. We retrospectively evaluated elite Italian athletes engaged in endurance or mixed sports disciplines selected for the 2023 European Games or 2024 Olympic Games. Athletes underwent blood tests, echocardiography, and cardiopulmonary exercise tests. We assessed the relationship between reticulocytes and the peak value of VO₂ (peak VO₂) and anaerobic threshold (AT). In addition, the effects of age, sex, haemoglobin concentration, stroke volume, peak heart rate, and reticulocytes on peak VO₂ and AT were assessed using multiple linear regression. Of the 105 athletes, reticulocyte count (0.059 ± 0.024 × 10¹²/L) negatively correlated with peak VO₂ (45.5 ± 9.1 mL/min/kg) (p = 0.022) and AT (27.6 ± 7.9 mL/min/kg) (p = 0.040). Using multivariate linear regression analysis, reticulocytes were independent predictors of peak VO₂ and AT (95% confidence interval: −192.3 to −45.9; p = 0.001; 95% confidence interval: −143.4 to −13.8: p = 0.018, respectively). Our findings indicated a negative relationship between reticulocyte count and peak VO₂ or AT. The life span of reticulocytes was close to the period of transient decline in RBC function that occurred after high-intensity exercise; therefore, the changes in reticulocytes might be related to the decline in exercise performance owing to this decline in RBC function. Full article

Background: High-dose γ-ray exposure (≥7 Gy) in nuclear emergencies induces life-threatening acute radiation syndrome, characterized by rapid hematopoietic collapse (leukocytes <0.5 × 10⁹/L) and gastrointestinal barrier failure. While clinical biomarkers like leukocyte depletion guide current therapies targeting myelosuppression, the concomitant metabolic disturbances and gut microbiota dysbiosis—critical determinants of delayed mortality—remain insufficiently profiled across the 28-day injury-recovery continuum. Methods: This study investigates the effects of ⁶⁰Co γ-ray irradiation on metabolic characteristics and gut microbiota in Sprague Dawley rats using untargeted metabolomics and 16S rRNA sequencing. Meanwhile, body weight and complete blood counts were measured. Results: Body weight exhibited significant fluctuations, with the most pronounced deviation observed at 14 days. Blood counts revealed a rapid decline in white blood cells, red blood cells, and platelets post-irradiation, reaching nadirs at 7–14 days, followed by gradual recovery to near-normal levels by 28 days. Untargeted metabolomics identified 32 upregulated and 33 downregulated plasma metabolites at 14 days post-irradiation, while fecal metabolites showed 47 upregulated and 18 downregulated species at 3 days. Key metabolic pathways impacted included Glycerophospholipid metabolism, alpha-linolenic acid metabolism, and biosynthesis of unsaturated fatty acids. Gut microbiota analysis demonstrated no significant change in α-diversity but significant β-diversity shifts (p < 0.05), indicating a marked alteration in the compositional structure of the intestinal microbial community following radiation exposure. Principal coordinate analysis confirmed distinct clustering between control and irradiated groups, with increased abundance of Bacteroidota and decreased Firmicutes in irradiated rats. These findings highlight dynamic metabolic and microbial disruptions post-irradiation, with recovery patterns suggesting a 28-day restoration cycle. Spearman’s rank correlation analysis explored associations between the top 20 fecal metabolites and 50 abundant bacterial taxa. Norank_f_Muribaculaceae, Prevotellaceae_UCG-001, and Bacteroides showed significant correlations with various radiation-altered metabolites, highlighting metabolite–microbiota relationships post-radiation. Conclusions: This study provides insights into potential biomarkers for radiation-induced physiological damage and underscores the interplay between systemic metabolism and gut microbiota in radiation response. Full article

(1) Background: Contagious ecthyma, also known as orf, is an epitheliotropic zoonotic disease caused by the orf virus (ORFV), primarily affecting the skin and mucous membranes of ruminants such as goats and sheep, leading to the formation of papules and pustules. Vaccination is the most effective way to prevent this disease in susceptible animals; however, traditional attenuated vaccines carry the potential risk of reversion to virulence. Therefore, there is an urgent need to develop safe and effective vaccines for the prevention and control of orf. (2) Methods: In this study, building upon the previously constructed ORFV three-gene deletion strain rGS14-TrypMut, we employed homologous recombination to knock out the VIL-10 gene and successfully constructed a four-gene deletion strain, rGS14-QuadMut. We evaluated its in vitro growth characteristics, safety, and protective efficacy in a challenge model. (3) Results: The in vitro results show that rGS14-QuadMut had a replication ability similar to that of other two-gene deletion strains, with good genetic stability. In in vivo experiments, compared to rGS14-TrypMut, rGS14-QuadMut caused only mild redness and swelling at the inoculation site, with a faster healing rate, indicating better safety. Additionally, rGS14-QuadMut induced strong differentiation of CD4⁺ and CD8⁺ T cells, increased the CD4⁺/CD8⁺ ratio, and primarily stimulated a Th1-type immune response, with significant changes in cytokine levels, including IL-8, IFN-γ, and IL-2. In the challenge protection experiment, both rGS14-QuadMut and rGS14-TrypMut provided 100% protective efficacy. In conclusion, rGS14-QuadMut demonstrated enhanced safety without compromising immune protection efficacy and is a promising candidate for an orf live vaccine strain. Full article

Erythropoiesis is increased in polycythemia vera (PV), with proliferation of erythroid precursors, and macrophages from erythroblastic islands play a key role in this process. Circulating monocytes were shown to perform some of the macrophage’s functions in normal conditions, but their participation during stress erythropoiesis, as in PV, is yet to be determined. In this study, we evaluated the monocytes from the blood of healthy donors or PV patients regarding their phenotype, involvement in the clearance of erythroid cells, and their expression of iron-related molecules. We showed that circulating monocytes from PV patients contained red blood cell-derived material, which correlated with a reduction in Sirp-ɑ expression, indicating that they play a role in erythroid cell clearance in PV. Both PV monocytes and PV erythroid cells seem to influence the increase in erythrophagocytosis. The enhanced expression of heme-oxygenase-1 and ferroportin post-phagocytosis suggests their capability for heme degradation and externalization of residual iron. Moreover, PV monocytes presented higher expression of CD169, CD163, and VCAM-1, which are involved with erythroid adhesion, and they influenced in vitro erythroid cell line differentiation, suggesting that they may interfere with erythropoiesis in PV. Our findings highlight the similarities between PV monocytes and macrophages of erythroblastic islands. These insights contribute to a deeper understanding of erythrophagocytosis and erythropoiesis in the disease, offering new perspectives for advances in the field. Full article

Background/Objectives: The present study evaluated the diagnostic utility of underutilized parameters derived from complete blood count (CBC) analysis in identifying late-onset neonatal sepsis (LOS). The parameters evaluated included the nucleated red blood cell count (NRBC), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), plateletcrit (PCT), and platelet-to-lymphocyte ratio (PLR). Methods: This was a retrospective, single-center, case-control study in a tertiary neonatal intensive care unit. The study included 38 neonates diagnosed with LOS, and 22 healthy control subjects. The data collected encompassed demographic characteristics, clinical findings, and laboratory values, including complete blood count (CBC)-derived parameters, C-reactive protein (CRP) levels, and blood cultures. Statistical analyses were performed to assess differences between groups and the diagnostic performance of key parameters via receiver operating characteristic (ROC) curves. Results: The results of the study are as follows: A set of notable discrepancies were identified in a number of parameters when comparing the LOS and control groups. Elevated levels of C-reactive protein (CRP), platelet count, platelet-to-lymphocyte ratio (PLR), lymphocyte percentage, and neutrophil-to-lymphocyte ratio (NLR) were found to be associated with LOS. Concurrently, decreased hemoglobin, hematocrit, neutrophil percentage, NRBC percentage, and NLR were also associated with LOS. PLR exhibited the most robust diagnostic efficacy, with a cutoff value of 45.24 attaining 81.6% sensitivity, 61.9% specificity, and an area under the curve (AUC) of 0.787 (95% CI: 0.671–0.903). The application of a logistic regression analysis indicated that the PLR emerged as the most salient independent predictor of LOS (odds ratio [OR]: 1.071; 95% confidence interval [CI]: 1.009–1.135; p = 0.023). Conclusions: CBC-derived parameters, particularly the PLR, have been shown to offer promising diagnostic value for LOS. These findings support the incorporation of these accessible and cost-effective biomarkers into clinical practice for the early diagnosis and management of LOS, warranting further validation in larger, multicenter studies. Full article

Background/Objectives: Sickle cell disease (SCD) is caused by a β-globin gene mutation (βGlu6Val) that produces sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, leading to red blood cell (RBC) sickling; therefore, hemoglobin is a central therapeutic target for SCD. Current strategies include increasing the levels of oxygenated HbS (which cannot polymerize) and/or directly destabilizing the deoxygenated HbS polymer. This study aimed to design and synthesize next-generation Michael acceptor antisickling hemoglobin modifiers (MMA-206, MMA-207, MMA-208, and MMA-209) and evaluate their antisickling efficacy. Methods: Four Michael acceptor compounds (MMA-206 to MMA-209) were synthesized and characterized. Their pharmacologic activities and modes of action were assessed in vitro using disulfide exchange reaction with normal hemoglobin, sickling inhibition assays with sickle red blood cells, and hemoglobin oxygen equilibrium curve analysis with normal and sickle red blood cells. Results: MMA-206 exhibited the strongest antisickling activity, outperforming previously studied Michael acceptor antisickling agents. All four MMA analogues bound to hemoglobin at βCys93, destabilizing the low-oxygen-affinity T-state and thereby preventing deoxygenation-induced HbS polymerization and RBC sickling. In addition, they appeared to directly destabilize the HbS polymer, indicating a second mechanism of action. Furthermore, time-dependent oxygen equilibrium measurements confirmed that their pharmacologic effect was sustained over time in vitro. Conclusions: The new Michael acceptor compounds, particularly MMA-206, demonstrated potent antisickling effects via dual mechanisms and showed sustained activity. These findings highlight Michael acceptor compounds’ promise as hemoglobin oxygen-affinity modulators for the treatment of SCD. Full article

Biocompatible nanocarriers were formulated by encapsulating medicinal extracts from Bryonia dioica (Red Bryony) and Glaucium leiocarpum (Horned Poppy) using a nanophytosome approach. The nanophytosomes were prepared by employing a thin-film hydration technique. The SEM results showed a broad size distribution for both nanophytosomes, and the encapsulation efficiency was about 75–80% for both Red Bryony and Horned Poppy nanophytosomes, as confirmed through scanning electron microscopy (SEM) and dynamic light scattering (DLS). Zeta potential analysis indicated sufficient surface charges to maintain colloidal stability. Encapsulation improved the release characteristics of the extracts, exhibiting an initial burst release followed by sustained release, which is advantageous for enhancing bioavailability within a liquid environment. Fourier-transform infrared (FTIR) spectroscopy identified key functional groups, confirming the successful encapsulation of bioactive ingredients within the nanophytosomes. Cytotoxicity tests on fibroblast cell lines (HSF-PI 16) demonstrated the safety of these nanocarriers, indicating biocompatibility at concentrations up to 200 μg/mL. Stability tests over 30 days revealed minimal size fluctuations, further supporting the structural integrity of the formulations. Results suggest that the synthesized nanophytosomes could serve as effective and novel nanocarriers for herbal delivery, addressing the bioavailability limitations of herbal extracts and offering a promising approach for therapeutic applications in both traditional and alternative medicine. This is the first study to report nanophytosome-based delivery of Red Bryony and Horned Poppy extracts. Full article

miR-211-5p exhibits dysregulated expression in various malignant tumors and has been implicated in the regulation of tumor cell proliferation, apoptosis, inflammation, and neurogenic processes. Previous studies have demonstrated that miR-211 negatively regulates ELOVL6, suggesting its involvement in lipid metabolism and lipogenesis within bovine adipose tissue. Our prior transcriptomic analysis revealed upregulated miR-211-5p expression in rabbits fed a high-fat diet, indicating its potential role in lipid metabolism regulation. However, the precise functions of miR-211-5p in lipid deposition and lipogenesis in rabbit preadipocytes remain unclear. To address this knowledge gap, this study utilized rabbit preadipocytes as experimental models to investigate the molecular mechanisms by which miR-211-5p regulates preadipocyte proliferation and differentiation. The findings aim to provide a theoretical basis for improving rabbit meat quality. The main findings of this study are summarized as follows: (1) The EdU proliferation assay, RT-qPCR detection, and CCK-8 cell viability assay revealed that overexpression of miR-211-5p inhibits the proliferation of rabbit preadipocytes, while inhibition of miR-211-5p expression promotes the proliferation of preadipocytes. (2) The precursor adipocytes were transfected and induced to differentiate. RT-qPCR, western blot (WB), and Oil Red O staining assays showed that overexpression of miR-211-5p promotes the maturation and differentiation of precursor adipocytes in meat rabbits, while inhibition of miR-211-5p expression inhibits the maturation and differentiation of precursor adipocytes in rabbits. (3) Through transcriptome sequencing, a total of 147 differentially expressed genes were identified. Among them, TPK1 is the target gene of miR-211-5p and is also the newly identified important gene involved in lipid synthesis. (4) After silencing the target gene TPK1, a series of experiments, including RT-qPCR, WB, Oil Red O staining, and CCK-8 cell viability assay, were conducted. The results showed that interfering with the expression of the TPK1 gene can inhibit the proliferation of rabbit preadipocytes and promote their differentiation. (5) After co-transfection of miR-211-5p inhibitor and si-TPK1, experiments such as EdU assay, RT-qPCR, western blot (WB), Oil Red O staining, and CCK-8 cell viability detection were conducted. It was found that miR-211-5p inhibits the proliferation and promotes the differentiation of rabbit preadipocytes by targeting TPK1. Full article

Fish red blood cells (RBCs) are nucleated, transcriptionally active, and key players in both gas transport and immune responses. They are the primary targets of Orthoreovirus piscis (PRV), the etiological agent of heart and skeletal muscle inflammation (HSMI), which includes three genotypes (PRV-1, PRV-2, and PRV-3), linked to circulatory disorders in farmed salmon. In Chile, PRV-3 affects the coho salmon (Oncorhynchus kisutch), but host–pathogen interactions remain poorly characterized. This study compared the interactions of PRV-3 in coho salmon and PRV-1 in Atlantic salmon (Salmo salar) using RBC infection models. RBCs were isolated from healthy juvenile salmon (n = 3) inoculated with either PRV-1 (Ct = 18.87) or PRV-3 (Ct = 21.86). Poly I:C (50 µg/mL) was used as a positive control for the antiviral response. Cells were monitored for up to 14 days post-infection (dpi). PRV-3 infection in coho salmon RBCs caused significant metabolic disruption, apoptosis from 7 dpi, and correlated with increasing viral loads. In contrast, PRV-1 infection in Atlantic salmon RBCs showed limited apoptosis and maintained cell viability. Coho salmon RBCs upregulated rig-i, mx, and pkr transcripts, indicating activation of the type I interferon pathway, whereas Atlantic salmon RBCs exhibited a more attenuated response. PRV-3 induced notable morphological changes in coho salmon RBCs, although neither PRV-3 nor PRV-1 caused hemolysis. These findings highlight species-specific differences in RBC responses to PRV infection and provide new insights into the pathogenesis of PRV-3 and PRV-1. Full article