Search Results (12,207)

Silver nanoparticle (AgNP)-based products have been increasingly applied in aquaculture due to their antimicrobial properties and capacity to modulate host immunity. This study investigated the biological activities of synthesized silver nanowires (AgNWs), with particular emphasis on their anti-Vibrio efficacy and immunomodulatory effects, to evaluate their potential application in shrimp aquaculture. Antibacterial activity was assessed using nonlinear regression analysis to determine minimum inhibitory concentrations (MICs) against three major Vibrio pathogens, while cytotoxicity and immune responses were evaluated using white shrimp hemocytes through cell viability assays and in vitro gene expression analysis, respectively. AgNWs exhibited antibacterial effects on Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi, with MIC values of 873.7, 58.78, and 672.1 μg/mL, respectively. Hemocyte viability remained above 90% at AgNW concentrations of up to 1000 mg/L, indicating good biocompatibility. AgNWs significantly upregulated immune-related lipopolysaccharide and β-1,3-glucan-binding protein (LGBP) and Toll gene expression at specific concentrations, indicating immunostimulation. These results suggest that AgNWs possess antibacterial activity and immunomodulatory potential with low cytotoxicity, supporting their promise as a novel functional agent for shrimp disease management. Full article

Subadult flathead grey mullets (Mugil cephalus) were fed three experimental diets containing increasing percentages of partially defatted black soldier fly (Hermetia illucens, BSF) that proportionally replaced the protein sources in the reference diet. At the end of the feeding trial, fish growth and gut, liver and spleen histology were evaluated. BSF inclusion did not significantly affect growth performances in any dietary groups. However, Fulton’s condition factor was lower in fish who were fed diets with the highest replacement levels (15% and 20%; BSF15 and BSF20) compared to those fed the 10% replacement (BSF10) and the control diet (BSF0). Histological analyses revealed increased villi thickness and mucous cell proliferation in the intestine of fish from BSF10 and BSF15 groups. A significant worsening of intestinal condition was observed in fish from the BSF20 group. Liver histology was not affected, while a dose-dependent effect on spleen was observed in fish fed BSF inclusions. Despite the absence of enteritis signs, an increase in macrophages/like TNF-α+ cells in the intestine mucosa indicated immune stimulation in the BSF10 group. Results indicate, for the first time, a threshold for BSF meal inclusion in diets specifically formulated for flathead grey mullets. The BSF10 diet was optimal, as growth performance was not affected and intestine health improved at both morphological and innate immune system levels. Full article

Objective: To evaluate the diagnostic and prognostic utility of the hemoglobin–albumin–lymphocyte–platelet (HALP) score and several systemic inflammatory indices derived from routine blood parameters—including the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), pan-immune inflammation value (PIV), and systemic inflammatory response index (SIRI)—for pathogen differentiation and clinical assessment in culture-proven late-onset neonatal sepsis (LOS). Methods: A retrospective analysis was conducted on a cohort of 150 neonates with culture-proven LOS. Systemic inflammatory indices were calculated at baseline (first week of life) and at the time of septic insult. The discriminative power of these indices was assessed via ROC curve analysis, with optimal cut-off points determined by the Youden Index. Risk stratification was performed using Odds Ratio (OR) modeling with 95% Confidence Intervals (CIs) to evaluate the predictive strength of each marker according to its respective threshold. Results: Diagnosis-phase assessments identified SII as the premier discriminator for microbiological etiology (AUC = 0.869; OR = 44.57), outperforming PLR and PIV. Although HALP demonstrated moderate efficacy in distinguishing pathogens, it lacked prognostic value regarding mortality. Conversely, SIRI displayed limited clinical utility, yielding the lowest predictive performance in our cohort. Conclusions: In neonatal sepsis, the HALP score provided additional clinical information when compared with several hematological inflammatory indices. Although HALP was not associated with mortality, prospective multicenter studies are needed to clarify the role of these cost-effective markers in pathogen differentiation and clinical assessment of LOS. Full article

Immunosuppression is associated with impaired immune responses and increased susceptibility to disease, highlighting the need for safe and effective immunomodulatory strategies. Oligosaccharides derived from natural sources have attracted growing interest due to their bioactivity and regulatory effects on host immunity. The present study was designed to evaluate the immune-enhancing potential of Periplaneta americana oligosaccharides (PAOSs) and to explore their association with SCFA-producing gut microbiota and metabolic regulation in an immunosuppressed mouse model. PAOS administration significantly increased serum immunoglobulin levels (IgG and IgM), promoted the secretion of immunoregulatory cytokines (IFN-γ, IL-2, TNF-α, IL-10, and IL-4), and elevated the proportion of CD4⁺ T cells in the spleen. In addition, PAOSs alleviated oxidative stress by reducing malondialdehyde accumulation while promoting the activity of key antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. Metabolomic analysis revealed that PAOSs altered host metabolic profiles, particularly enhancing pyrimidine metabolism. Furthermore, PAOSs markedly enriched short-chain fatty acid (SCFA)-producing bacteria, and elevated colonic short-chain fatty acid levels. These changes were closely associated with the observed improvement in immune function. Collectively, this study demonstrated that PAOSs exerted immunomodulatory effects through coordinated regulation of SCFA-producing gut microbiota and host metabolism, elucidating the mechanisms underlying the bioactivity of insect-derived oligosaccharides. Full article

The programmed death-ligand 1 (PD-L1) plays a critical role for promoting cancer immune evasion. However, the resistance to PD-L1-targeted immunotherapy greatly limits its application. α-lipoic acid (ALA) is an endogenous antioxidant, while whether ALA affects PD-L1 expression remains unknown. In IFN-γ-stimulated castration-resistant prostate cancer (CRPC)-mimicking PC3 and DU145 cells, the expression of PD-L1 and its regulatory genes was determined by Western blotting, RT-PCR, and immunofluorescence. The T-cell-mediated tumor-killing activity was evaluated in a co-culture system of cancer cells and Jurkat T cells. ALA significantly inhibits IFN-γ-induced PD-L1 protein and mRNA expression without affecting its degradation. The upstream genes accounting for PD-L1 induction, including JAK1/STAT1/IRF-1 cascade, c-Myc, HIF-1α, and GSK3β activity, were markedly suppressed by ALA. The decreased expression of PD-L1 and these regulators by ALA is also modulated by attenuation of mTOR/p70S6K/4EBP1-dependent protein translation and ROS production. In the co-culture system, ALA markedly increased T-cell-mediated tumor-killing activity compared to that of ALA treatment alone, suggesting that ALA may augment the antitumor immunity. Collectively, we demonstrated that ALA-mediated inhibition of PD-L1 expression is regulated by multiple mechanisms, which indicates that ALA may be a potential agent to enhance cancer immunotherapy, particularly in CRPC. Full article

Background: Preoperative differentiation between uncomplicated and complicated paediatric appendicitis remains challenging. This study aimed to evaluate the diagnostic performance of routine admission biomarkers and blood cell count-derived inflammatory indices for severity stratification and to determine whether fibrinogen provides additional predictive value beyond commonly used markers. Methods: We conducted a retrospective single-centre study (2018–2025) using electronically recorded clinical data. Patients with suspected appendicitis were identified through appendicitis-related ICD-10 codes and diagnostically validated. The final analytical cohort required complete admission laboratory data, including C-reactive protein (CRP), fibrinogen, and complete blood count parameters. Derived inflammatory indices included the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII). Diagnostic discrimination and multivariable prediction models were evaluated to assess the ability of these markers to distinguish complicated from uncomplicated appendicitis. Results: Of 1518 screened records, 1132 patients met inclusion criteria (620 complicated; 512 uncomplicated). Complicated appendicitis was associated with higher inflammatory markers and longer hospital stay (all p < 0.001). CRP demonstrated the strongest univariable discrimination (area under the curve [AUC] 0.785), while fibrinogen showed lower performance (AUC 0.744). A combined model including CRP, NLR, and SII achieved good discrimination (AUC 0.812), with minimal improvement after adding fibrinogen (AUC 0.813). In multivariable analysis, log-transformed CRP and SII remained independently associated with complicated appendicitis (both p < 0.001). A rule-out probability threshold of 0.303 achieved 90% sensitivity (negative predictive value 0.803), whereas a CRP cut-off ≥92.24 mg/L showed high specificity (0.943) and positive predictive value (0.900). Conclusions: Routine admission biomarkers and inflammatory indices derived from complete blood counts can support severity stratification in paediatric appendicitis. CRP and SII provide meaningful predictive information, whereas fibrinogen contributes little additional discriminatory value beyond CRP-based models. These findings suggest that a small set of routinely available laboratory markers may assist early risk stratification, although external validation is required before clinical implementation. Full article

Tributyltin (TBT) is well known for inducing imposex in mollusks. Studies have shown its hepatotoxicity and immunotoxicity in laboratory animals, with macrophages playing a crucial role in maintaining hepatic homeostasis and influencing disease progression; however, no research has yet explored its effects on hepatotoxicity and immunotoxicity based on hepatic macrophages. To address this gap, weaned rats were treated with corn oil or TBT (0.5, 5, or 50 μg/kg) via oral gavage every three days for 60 days. Liver sections were then subjected to hematoxylin and eosin staining, Oil Red O staining, Sirius Red staining, immunohistochemistry, and immunofluorescence to assess the effects of TBT. Hepatic function and inflammatory state were evaluated by serum biochemistry and quantitative reverse transcription-PCR (qPCR), respectively. Histological examination indicated that TBT exposure did not increase hepatic lipid accumulation but resulted in hepatocyte edema and congestion in the 5 and 50 μg/kg groups, accompanied by progressive hepatic fibrosis. In parallel, 50 μg/kg TBT increased the number of macrophages, driven by an increase in the CD206⁺CD68⁺ subset. qPCR analysis revealed a significant decrease in the expression of pro-inflammatory cytokines (such as IL-1β and TNF-α), confirming an immunosuppressive state in the livers of rats exposed to TBT. Moreover, the significant increase in serum ALT activity further revealed hepatic injury induced by 50 μg/kg TBT. In summary, TBT exposure restructures the hepatic immune microenvironment, promoting the progression of liver fibrosis independently of fat accumulation in rats. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and systemic inflammation, with the cardiovascular (CV) system representing a major yet frequently under-recognized target. Cardiac involvement spans from subclinical myocardial inflammation to overt pericardial disease, myocarditis, valvular abnormalities, coronary microvascular dysfunction, and accelerated atherosclerosis. Given that CV disease remains a leading cause of morbidity and mortality in SLE, early detection of silent cardiac injury is crucial. Aim: This review aims to provide a comprehensive and clinically oriented overview of CV involvement in SLE, focusing on the role of multimodal cardiac imaging in the detection, characterization, and risk stratification of cardiac abnormalities, as well as its potential implications for clinical management and preventive strategies. Methods: This narrative review is based on a structured, non-systematic search of PubMed (2013–2026), combining the term “systemic lupus erythematosus” with imaging-related keywords including “transthoracic echocardiography,” “cardiac magnetic resonance,” and “cardiac computed tomography.” English-language studies in adult populations were screened and selected according to clinical relevance, methodological robustness, and contribution to understanding SLE-related cardiac involvement. Discussion: Multimodal cardiac imaging plays a central role in the evaluation of SLE-related cardiac disease. Transthoracic echocardiography (TTE) represents the first-line modality for the assessment of ventricular function, pericardial disease, and valvular abnormalities, while deformation imaging enables the detection of subtle myocardial dysfunction. Cardiac magnetic resonance (CMR) provides comprehensive tissue characterization, allowing differentiation between active inflammation and chronic fibrosis. Cardiac computed tomography (cCT) identifies subclinical coronary atherosclerosis and high-risk plaque features, whereas nuclear imaging techniques offer insight into inflammatory activity and microvascular dysfunction. Conclusions: An integrated, imaging-based approach enables early diagnosis, refined CV risk stratification, longitudinal monitoring, and personalized therapeutic strategies. Multimodal imaging thus represents a key pillar of precision medicine in lupus-associated CV disease. Full article

Background: MicroRNAs (miRNAs) are stable, small non-coding RNAs involved in asthma-related pathways and are promising diagnostic biomarkers and therapeutic targets in childhood asthma. Objective: To identify miRNAs differentially expressed in preschool wheezing and childhood asthma, evaluate their association with asthma diagnosis and severity-related phenotypes, and explore their potential translational relevance through exploratory bioinformatic analyses. Methods: A systematic search of Medline, Embase, SCOPUS, PubMed, CINAHL, and Web of Science was conducted for English-language articles published up to March 19, 2025. Eligible human studies reported that miRNAs were differentially expressed in children with wheeze or asthma versus healthy controls (p < 0.05, fold change ≥ 1.5). Bioinformatic analysis identified hub genes, constructed protein–protein interaction networks, and predicted drug–gene interactions. Results: Forty-seven studies met the inclusion criteria, yielding 58 differentially expressed miRNAs (31 up, 27 down). Recurrently reported miRNAs included miR-497, let-7e, miR-98, miR-21, miR-126a, miR-196a2, miR-1, miR-146a-5p, miR-210-3p, miR-145-5p, and miR-200c-3p across blood, nasal swabs, BALF, and exhaled breath condensate. miR-26a showed strong diagnostic performance (sensitivity 83%, specificity 93%; p < 0.002, 95% CI 0.831–0.987). Functional enrichment implicated 56 differentially expressed genes in metabolic and immune processes. Ten hub genes (including TNF, IL5, IL13, TLR4) were linked to 339 potential therapeutic agents; the exploratory network analysis highlighted overlap between predicted miRNA-regulated hub genes and existing asthma-relevant drug targets, including approved biologics. Conclusions: Our review findings suggest that several miRNAs are promising candidate biomarkers for childhood asthma phenotyping and severity assessment; however, their diagnostic utility remains exploratory and requires rigorous external validation and standardisation before clinical application. Full article

Background/Objectives: Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and the high prevalence of malignant ascites, a hallmark of advanced disease that is difficult to control and contributes to immune suppression and treatment failure. Despite advances in standard care, durable responses are rare. This study investigates a novel immunotherapeutic strategy designed to overcome the suppressed peritoneal microenvironment using an oncolytic vaccinia virus engineered to express a decoy-resistant IL-18 mutein. Methods: We generated a vaccinia virus (vvDD-nsmDR-18) expressing a non-secreted, mature, decoy-resistant IL-18. Viral expression was validated via RT-qPCR and fluorescence microscopy, while cytotoxicity was confirmed using CCK-8 assays. The antitumor efficacy of vvDD-nsmDR-18 was evaluated in the aggressive murine ID8a ovarian cancer model. The underlying mechanisms of action were investigated using flow cytometry and transcriptional profiling. Results: Treatment with vvDD-nsmDR-18 significantly prolonged survival and was associated with reduced abdominal distension consistent with decreased ascites burden. Immune analyses indicated enhanced T cell activation across multiple anatomical compartments, including tumors, peritoneal cavity, and spleens, the latter recently suggested to serve as a reservoir for tumor-reactive T cells. This systemic activation was characterized by increased IFN-γ and perforin expression. In addition, vvDD-nsmDR-18 treatment was associated with expansion of CD39⁺CD103⁺CD8⁺ tumor-reactive T cells and a shift toward a lower PD-1 expression phenotype within this population. Conclusions: These findings demonstrate that nsmDR-18-expressing oncolytic viruses can remodel the immunosuppressive landscape of advanced ovarian cancer, suggesting this approach is a promising candidate for further clinical development. Full article

Background: Cardiovascular complications stemming from diabetes pose a grave threat to patients’ survival. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) significantly increase the risk of heart failure, yet no reports have clarified whether there are differences in the pathway alterations involved in these two conditions. Investigating the heterogeneity of the cardiac remodeling between these two types of diabetes is conducive to reducing the incidence of cardiovascular events in diabetic patients in clinical practice. Methods: T1D and T2D models were established in adult mice, and the hearts were collected for RNA sequencing. Differential expression analysis (DEA) was performed. Integrating functional enrichment analyses, we probed into gene and pathway heterogeneity. Subsequently, we compared single-cell RNA sequencing (scRNA-seq) data of hearts from T1D and T2D mice, focusing on three cell populations (endothelial cells, macrophages, and fibroblasts) to identify gene and pathway differences. Finally, we evaluated shared genes and common signaling pathway changes across these three cell populations in both diabetes types. Results: We have successfully established T1D and T2D models in mice. Compared with shared genes, the two types of diabetes had more consistent pathway changes. Further scRNA-seq analysis identified endothelial cells, macrophages, and fibroblasts as significantly associated with the diabetic phenotype. In shared pathway, endothelial cells were significantly enriched in pathways related to endothelial proliferation and angiogenesis; macrophages were enriched in immune response pathways; and fibroblasts were enriched in pathways involving fibrosis, cell proliferation, and apoptosis. In endothelial cells, inflammatory response and fatty acid metabolism pathways were predominantly enriched in T1D, while energy metabolism pathways were dominant in T2D. In macrophages, antiviral immune pathways were specifically enriched in T1D, whereas macrophages in T2D were additionally implicated in the regulation of cardiomyocyte function. In fibroblasts, immune-related pathways were characteristically enriched in T1D, while cell respiration and energy supply pathways were prominent in T2D. Common functional enrichment pathways across the three cell types in both diabetes types mainly involved innate immune responses and cardiac morphogenesis, with the proportion of shared pathways being significantly higher than that of shared genes. Conclusions: This study, by combining RNA sequencing and scRNA-seq, revealed that cardiac pathologies induced by T1D and T2D exhibit a higher degree of consistent pathway changes compared to shared gene changes. Interventions targeting these common pathways may hold greater value in preventing and treating diabetic cardiomyopathy. Full article

The porcine epidemic diarrhea virus (PEDV) causes a gastrointestinal disease generating mortality rates approaching 100% in piglets worldwide. The S glycoprotein of PEDV is the main target for the development of vaccines. Two vaccines approved by the Ministry of Agriculture and Rural Development are used in Mexico: the first vaccine is based on an inactivated virus isolated more than a decade ago, whereas the second vaccine is based on mRNA technology. The most important tool for controlling PEDV outbreaks is vaccination; however, coronaviruses are characterized by the accumulation of multiple mutations, which compromise the immune response elicited by outdated vaccines. In this work, we classified the Mexican strains of PEDV reported so far in GenBank, according to their genotypes. Subsequently, we searched for B and T cell epitopes conserved in Mexican PEDV strains using bioinformatic tools. In addition, we explored whether these epitopes can induce allergies, autoimmunity, and/or toxic effects. Next, we determined the localization of B cell epitopes in the S glycoprotein using the protein crystal and protein modeling of several S glycoproteins. Finally, we carried out molecular docking analysis to assess whether these T cell epitopes could interact with the peptide-binding groove of the Swine Leukocyte Antigens (SLAs). Five conserved B cell epitopes were found to be exposed on the surface of the S glycoprotein, whereas several promiscuous CTL and HTL epitopes were bound, with low free energy, to the peptide-binding grooves of SLA-I and SLA-II, respectively. The best epitopes were used to generate a plasmid carrying the sequence to produce a recombinant protein. This plasmid was used for transfection experiments in PK-15 cell culture. The B cell epitopes reported here were recognized by the sera from pigs infected with PEDV but not by the sera from uninfected animals. These results justify future evaluations of the ability of these epitopes to stimulate cytokine production by T cells, antibody generation, and their neutralizing activity. Full article

Background: Patients with diabetes mellitus exhibit increased susceptibility to peri-implant inflammation and implant failure due to systemic metabolic dysfunction, impaired immunity, and delayed tissue healing. The oral microbiome is increasingly recognized as a key intermediary in these pathogenic processes. Aims: This review aims to systematically evaluate the available literature examining the relationships among the oral microbiome, biomaterial biocompatibility, and inflammatory changes in peri-prosthetic tissues in insulin-dependent diabetic patients. Methods: A systematic search of PubMed and Scopus databases identified studies published between January 2000 and July 2025. Eligible studies (25 in total) included clinical, histological, microbiological, or immunohistochemical investigations involving diabetic patients rehabilitated with dental implants or prostheses. Study selection and reporting followed PRISMA 2020 guidelines. Results: Diabetic cohorts showed consistent microbial alterations, including a higher relative abundance of periopathogenic species (P. gingivalis, T. forsythia, and F. nucleatum), lower microbial diversity, and greater biofilm-forming potential. Histological analyses frequently described increased inflammatory infiltrates, higher cytokine expression, and reduced soft-tissue integration. Biomaterial surface characteristics were also associated with differences in microbial adhesion, while hyperglycemia was linked to microbial and host-response patterns suggestive of greater pathogenicity and inflammation. Collectively, these findings suggest that diabetes-associated dysbiosis may be associated with increased peri-implant inflammatory changes and altered peri-implant homeostasis. Conclusions: The oral microbiome may be involved in inflammatory activity and biocompatibility at the tissue–implant interface in diabetic patients. A better understanding of host–microbe–material interactions may support risk assessment and help inform future personalized management strategies, such as targeted antimicrobial approaches, probiotic modulation, and biomaterial surface optimization, although these implications should be interpreted cautiously given the predominantly observational and heterogeneous nature of the available evidence. Full article

Lichen planus (LP) is a chronic immune-mediated inflammatory disease of unknown etiology affecting the skin and mucous membranes and is frequently associated with comorbid conditions, although data from Swedish populations remain limited. This retrospective population-based case–control study included all registered citizens in Region Jönköping, Sweden, between 2013 and 2022, to examine comorbidities, estimate prevalence and incidence, assess diagnostic validity of ICD-10 coding (L43), and evaluate treatment patterns. Incidence and prevalence were calculated, demographic and treatment characteristics were described, and diagnostic validity was assessed through independent medical record review of 70 randomly selected cases to determine positive predictive value (PPV). Associations between LP and predefined comorbidities were analyzed using binomial logistic regression adjusted for age and sex. Among 361,812 individuals, prevalence was 235.5 and incidence 19.6 per 100,000 inhabitants. The PPV of the LP diagnosis was 78.6%, yielding an adjusted prevalence of 184.9 per 100,000 inhabitants. Over one third of prevalent patients received topical therapy, primarily corticosteroids. LP was significantly associated with thyroid, malignant, metabolic, and autoimmune conditions. LP is relatively uncommon, ICD-10 coding shows acceptable validity, and its association with clinically relevant comorbidities highlights the need for comprehensive patient assessment. Full article

Bcakground: Hepatocellular carcinoma (HCC) is a prevalent malignancy with limited therapeutic options. Drug repurposing offers an attractive strategy to accelerate anticancer discovery. The pleuromutilin class of antibiotics, including the human-approved agent lefamulin and the veterinary drug tiamulin, has shown preliminary anticancer potential, but its efficacy and mechanism in HCC remain unexplored. Methods: The anti-tumor effects of lefamulin and tiamulin were evaluated in HCC cell lines, patient-derived organoids, and a C57BL/6 mouse subcutaneous tumor model. Safety was assessed in a human normal hepatocyte cell line and by histopathological examination of major organs in treated mice. Mechanistic investigations were performed using RNA-sequencing, RT-qPCR, immunohistochemistry (IHC), filipin staining, pharmacological rescue assays, and shRNA-mediated gene silencing. Results: In this study, we found that both lefamulin and tiamulin markedly inhibited HCC cell proliferation in vitro and significantly suppressed tumor growth in vivo (lefamulin vs. control, p = 0.014; tiamulin vs. control, p = 0.021), without causing significant toxicity. RNA-sequencing analysis revealed consistent downregulation of the cholesterol transporter Abca1 (ATP-binding cassette transporter A1) and alterations in cell adhesion molecule pathways. Functional studies confirmed that treatment reduced ABCA1 protein levels, leading to intracellular cholesterol accumulation and aberrant distribution. Furthermore, treated tumors exhibited a significant increase in CD8⁺ T-cell infiltration, with CD4⁺ T cells and macrophage infiltration remained unchanged, indicating a specific modulation of the tumor immune microenvironment. Conclusions: These findings suggest that lefamulin and tiamulin are promising therapeutic candidates for HCC. Full article