Search Results (384)

African swine fever virus (ASFV) is an important transboundary animal pathogen with significant impacts on the global swine industry. Overwhelming proinflammatory responses are a major virulence mechanism for ASFV, but the dynamics of these changes during clinical disease are not completely understood. We constructed a detailed portrait of the innate immune responses during acute African swine fever (ASF) at the cellular, transcriptomic, and cytokine levels. Samples serially obtained from infected piglets show that progression of acute ASF is characterized by rapid increases in plasma type I interferons, TNF-α, IL-12p40, and IL-10, which coincide with the manifestation of clinical disease and viral DNAemia. Lymphocytes and natural killer (NK) cells progressively declined, with fluctuations in B cell, CD8+ T cell, and CD4+/CD8+ T cell populations. Blood monocytes and macrophages were highly variable throughout infection, with an abrupt spike in CD203+ mature macrophages immediately prior to death. Transcriptomic analysis of blood showed downregulation of cellular translation as early as 1 day post-challenge (DPC) and significant upregulation of antiviral immune processes at 5 DPC and 7 DPC, which overlapped with the onset of clinical disease. Together, these results present a detailed delineation of fatal ASF which involves an initial infection and damage of susceptible myeloid cells prior to symptomatic disease characterized by pro-inflammatory immune responses, lymphoid depletion, and clinical deterioration. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disease with heterogeneous clinical manifestations and uncertain systemic immune involvement. This study aimed to characterize peripheral immune profiles and circulating tumor markers in women with ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE), and to explore their associations with disease severity, symptom burden, and physical health perception. Peripheral blood leukocyte subsets, plasma cytokines, and tumor markers (CA125, CA19-9, CEA, HE4) were analyzed in 146 patients and 50 healthy controls. OE was associated with increased monocyte counts and reduced neutrophil proportions, while DIE showed elevated levels of IL-8 and Galectin-1. IL-33 levels correlated negatively with the revised American Society for Reproductive Medicine (rASRM) scores and positively with neutrophil proportion, suggesting a role in systemic immune regulation. Tumor marker levels varied by subtype: CA19-9 was higher in OE, and CEA in DIE. CA125 correlated with disease severity, and CEA with monocyte levels. Exploratory heatmaps revealed consistent immune-tumor associations linked to anatomical severity and symptom profiles. Although exploratory, these findings highlight the presence of distinct systemic immune patterns in endometriosis and support the potential of integrative blood-based biomarkers for future diagnostic and stratification strategies. Full article

Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4⁺ Th1 and CD8⁺ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8⁺ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article

A novel heterobimetallic ruthenium(II)–gold(I) complex featuring a bridging bis(diphenylphosphino)butane (dppb) ligand was prepared and fully characterized. Single-crystal X-ray diffraction revealed a piano-stool geometry around Ru(II) with η⁶-cymene, two chlorido ligands, and one phosphorus atom from dppb, while the Au(I) center adopts a linear P–Au–Cl coordination. Structural integrity in the solution was confirmed by 1D and 2D NMR spectroscopy, while solution behavior was further monitored by variable solvent ³¹P NMR and UV/Vis spectroscopy, indicating that the organometallic Ru–arene core remains intact, whereas the chlorido ligands coordinated to Ru exhibit partial lability. Complementary characterization included elemental analysis, FTIR, and UV/Vis spectroscopy. Spectrofluorimetric and FRET analyses showed that Au(dppb), Ru(dppb), and the heterobimetallic AuRu complex bind to BSA with apparent constants of 1.41 × 10⁵, 5.12 × 10², and 2.66 × 10⁴ M⁻¹, respectively, following a static quenching mechanism. In vivo biological evaluation in Wistar rats revealed no significant hepatotoxicity or nephrotoxicity, with only mild and reversible histological alterations and preserved hepatocyte nuclear morphology. Hematological analysis indicated a statistically significant reduction in leukocyte populations, suggesting immunomodulatory potential, while elevated serum glucose levels point to possible endocrine or metabolic activity. These findings highlight compound structural stability and intriguing bioactivity profile, making it a promising platform for further organometallic drug development and testing. Full article

Objective: This study aimed to analyze the epidemiological, hematological, and oxidative stress profile of truck drivers. Method: It involved 63 drivers from the western border of a state in southern Brazil who completed a questionnaire, had vital signs and anthropometric evaluations, and provided blood samples. Hematological parameters, leukocytes, and oxidative damage to proteins and lipids were analyzed. Results: A high prevalence of overweight and obesity was found among the drivers, with an increased risk of cardiovascular issues and hypertension. Obese drivers had higher monocyte counts, while those with normal weight had increased protein carbonylation levels. Conclusions: It is crucial to implement health interventions to prevent chronic diseases in truck drivers, given their high exposure to risk factors. Full article

Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease, marked by considerable clinical and molecular heterogeneity. While several genetic drivers have been linked to familial ALS (fALS), the biology of sporadic ALS (sALS)—which accounts for the majority of ALS cases—remains poorly defined. To address this gap, we analyzed 247 bulk mRNA-sequenced post-mortem tissue samples from the lumbar spinal cord and motor cortex and compared expression profiles between fALS, sALS, and controls. Variance-stabilized DEGs from DESeq2 analysis were used as inputs for weighted gene co-expression network analysis (WGCNA). Finally, gene ontology was used to identify transcriptomic signatures and biological pathways unique to sALS and fALS. In the spinal cord, sALS samples exhibited specific downregulation of mitochondrial complex I subunits (e.g., NDUFS8 and NDUFB7) and regulatory genes (e.g., AURKAIP1 and ATP5F1D), suggesting compromised metabolic resilience. In the motor cortex, a co-expression module associated with adaptive immune function and leukocyte infiltration was downregulated in sALS yet upregulated in fALS, indicating distinct inflammatory pathways between these two forms of ALS. Together, our findings highlight that while sALS and fALS are largely the same disease, they exhibit distinct transcriptomic signatures. By accounting for mode of inheritance in study designs—particularly sALS, which represents ~90% of ALS cases—researchers may reveal deeper insights into ALS pathology. This perspective could enable more targeted therapeutic strategies, ultimately improving outcomes for all ALS patients. Full article

Background: Various studies have shown that viral pneumonia pathogens display distinct inflammatory profiles, and hematological indices, such as the Neutrophil/Lymphocyte Ratio (NLR), Lymphocyte/Monocyte Ratio (LMR), and Platelet/Lymphocyte Ratio (PLR), can serve as accessible markers of disease severity. Moreover, the seasonal distribution of respiratory viruses appears to have shifted during the COVID-19 pandemic. Methods: This retrospective case–control study was conducted on patients diagnosed with PCR-confirmed viral pneumonia in the emergency department of a tertiary care center between 1 January and 31 December 2024. The control group comprised age- and sex-matched individuals without viral pneumonia. Subjects with comorbidities or ongoing treatments potentially affecting hematological indices were excluded. Seasonal distribution of viral pathogens was recorded. Hematological and inflammatory parameters at admission—including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR)—were evaluated. The associations between these biomarkers, Pneumonia Severity Index (PSI) scores, and hospitalization status were statistically analyzed. Results: In this study, it was determined that Influenza A/B was more common in winter (67.3%) and SARS-CoV-2 in summer (70.7%). The relationship between the Pneumonia Severity Index and hemogram parameters was examined in determining the severity of pneumonia. In SARS-CoV-2, leukocyte and neutrophil counts were positively correlated (R: 0.392, p: 0.003; R: 0.466, p: <0.001), while in Influenza A/B, lymphocyte, platelet, and monocyte counts showed a negative correlation (R: −0.402, p: 0.005; R: −0.331, p: 0.021; R: −0.327, p: 0.023). Correlations were found between inflammation parameters and the Pneumonia Severity Index, except for the Lymphocyte/Monocyte Ratio, between SARS-CoV-2 and Influenza A/B (p < 0.05). Conclusions: The seasonal distribution of viral pneumonia pathogens has been revealed following the COVID-19 pandemic. Due to differences in inflammation patterns in viral infections, different leukocyte subgroups have been suggested as biomarkers. Full article

Background: While economically vital, buffalo exhibits low reproductive efficiency largely due to embryonic losses during implantation. Successful implantation requires precise embryo–maternal communication and metabolic/immune adaptations in the endometrium. We aimed to identify key serum metabolic signatures and associated peripheral immune responses that characterize the endometrial receptivity window during early pregnancy in water buffalo. Methods: Blood samples from pregnant (Preg, n = 12) and non-pregnant (Non-P, n = 10) buffaloes were collected on days 15, 18, and 21 post-artificial insemination (AI). We measured leukocyte counts and hormone levels and performed untargeted serum metabolomic profiling using LC-MS. Results: Pregnant buffaloes showed significantly reduced total white blood cell count, lymphocyte (LYM%), and neutrophil (NEU%) percentages, indicating immune remodeling at the beginning of pregnancy establishment. Metabolomic analysis identified 131 differentially expressed metabolites (DEMs) associated with pregnancy status at different stages. Enriched pathways included steroid hormone synthesis, retinol metabolism, starch/sucrose metabolism, and phenylalanine biosynthesis. Crucially, alterations in unsaturated fatty acids, retinol, and phenylalanine metabolism, along with monocyte (MON%)/LYM% ratios, were strongly linked to receptivity changes and successful implantation. Conclusions: Endometrial receptivity in buffalo during the embryonic implantation window was associated with changes in immune cells and metabolism in the blood, suggesting that immunometabolism may play an essential role in modulating endometrial receptivity during the implantation window. This study provides potential clues and a metabolic framework for understanding the underlying mechanisms of buffalo embryonic implantation. Full article

Jellyfish stings induce a range of symptoms, from localized irritation to life-threatening systemic reactions, yet the underlying immune mechanisms remain poorly understood. This study employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from a severely affected patient and healthy controls, uncovering the immune landscape at single-cell resolution and identifying the signaling pathways. We identified 11 major immune cell types, with a marked increase in CD14+ monocytes (81.86% of total cells) and significant reductions in T cells, B cells, and CD16+ monocytes in the envenomated patient. Subclustering revealed six monocyte and four neutrophil subsets, each displaying distinct functional profiles. Patient monocytes were enriched for MMP9+ and RETN+ subsets, associated with leukocyte migration and inflammation, whereas healthy controls exhibited CD74+ monocytes linked to oxidative phosphorylation. Neutrophils in the patient were predominantly LTF+ and S100A12+, implicating inflammatory and immune regulatory pathways. These findings provide a detailed single-cell atlas of immune dysregulation post-jellyfish sting, highlighting the pivotal roles of MMP9+ monocytes and S100A12+ neutrophils in driving inflammation. This study offers potential therapeutic targets for mitigating severe immune responses in jellyfish envenomation. Full article

Fracture healing failure affects millions globally, yet early molecular mechanisms remain poorly understood. This study aimed to characterize initial fracture response through analyzing peripheral blood hematology, multiplex cytokine profiles, and microRNA (miRNA) expression in fracture hematoma within the first 5 days post-injury. In a prospective cohort of 64 patients with acute clavicle fractures, we assessed hematological parameters, cytokine levels via multiplex immunoassays, and miRNA expression through RNA sequencing, and quantitative PCR (qPCR) validation. Fracture severity and time elapsed post-injury were key drivers of molecular response variability. Severe fractures (type C) were associated with older patient age and impaired hematological parameters, including reduced hemoglobin, erythrocyte counts, and hematocrit. Leukocyte counts declined over time, reflecting evolving systemic inflammation. Severity-dependent cytokines included eotaxin, interferon alpha-2 (IFNα2), interleukin-1 alpha (IL-1α), macrophage inflammatory protein-1 (MIP-1α), whereas interferon gamma-induced protein 10 (IP-10) and MIP-1α distinguished temporal healing phases. MiRNA profiling revealed 55 miRNAs with significant time-dependent expression changes (27 downregulated, 28 upregulated). Five key miRNAs (miR-140-5p, miR-181a-5p, miR-214-3p, miR-23a-3p, miR-98-5p) showed robust temporal patterns and enrichment in cytokine signaling pathways critical for bone repair. This work presents the first detailed molecular portrait of early human fracture healing, highlighting hematological, immune cytokine, and miRNA networks orchestrating repair. These insights provide a foundation for biomarkers development to predict healing outcomes and support precision-targeted interventions in fracture management. Full article

Perfluorooctane sulfonate (PFOS), a member of the per- and polyfluoroalkyl substance (PFAS) family, has been associated with adverse health effects, including potential links to autism spectrum disorder (ASD). This study investigates the impact of PFOS on metabolic, immunologic and behavioral profiles in BTBR-mt^B6 mice, a mouse strain that models ASD, to provide insights into the role of PFOS in ASD development and related health concerns. Three-month-old male and female BTBR-mt^B6 mice were divided into two groups (n = 6) and received daily administration of either 1 mg/kg PFOS or vehicle over a three-month period by gavage. Metabolic assessments included measurements of body weight and weekly blood glucose levels, glucose and insulin tolerance tests, organ weights, and body compositions (free fluid, fat and lean tissue). Immune profiling was conducted via flow cytometric analysis of splenic leukocytes, while behavioral evaluations included grooming, sniffing, and three-chamber social interaction tests. PFOS exposure disrupted glucose homeostasis, with both sexes exhibiting elevated blood glucose levels. Male mice showed impaired glucose tolerance, delayed glucose level recovery, and increased insulin resistance, while females displayed decreased insulin resistance. Additionally, PFOS exposure led to liver enlargement in both sexes. Behavioral assessments revealed heightened grooming in PFOS-treated males, commonly interpreted as stress- or ASD-related repetitive behaviors, whereas females exhibited reduced grooming, reflecting altered behavioral responses to exposure. Immune alterations were also sex specific. PFOS-treated males exhibited decreased granulocytes, increased macrophages, and enhanced surface expressions of B220 and CD40L. PFOS-treated females showed increased macrophages, B-cells, cytotoxic T-cells and CD25⁺ T-cell subsets, with enhanced surface expression of B220 and CD8, and reduced surface expression of Mac-3. In addition, PFOS exposure reduced spleen weight in females. Taken together, PFOS exposure induced significant physiological and behavioral changes in BTBR-mt^B6 mice, with sex-specific differences observed. These results raise concern that PFASs may contribute to the development or exacerbation of metabolic, immune and neurodevelopmental disorders, highlighting the need for sex-specific human risk assessment in environmental toxicology. Full article

Background and Objectives: Dyslipidemia, a modifiable cardiovascular risk factor, is associated with chronic low-grade inflammation. While leukocyte-derived indices have been investigated in this context, eosinophil-related inflammatory markers remain underexplored. This study examined patterns of eosinophil-to-lymphocyte ratio (ELR) and eosinophil-adjusted systemic inflammation response index (EA-SIRI) across dyslipidemia phenotypes. Materials and Methods: In this retrospective study, adult subjects were classified into six dyslipidemia phenotypes. Leukocyte-derived indices were evaluated across groups, and analyses included comparisons of medians, prevalence rates, tertile distributions, odds ratios, and risk estimates. Results: Both ELR and EA-SIRI were significantly higher in individuals with atherogenic dyslipidemia (ELR: 0.18; EA-SIRI: 1.53) and combined dyslipidemia (ELR: 0.17; EA-SIRI: 1.49) compared to the normolipidemic group (ELR: 0.11; EA-SIRI: 0.92). Notably, these patterns were more pronounced in males aged <40 years and younger females (<40), suggesting sex- and age-related variations in eosinophil-related inflammatory responses to dyslipidemia. Moreover, the highest tertiles of both ELR and EA-SIRI exhibited higher triglycerides and lower HDL-C compared to the lowest tertiles (p < 0.001). The odds of atherogenic dyslipidemia were more than doubled in individuals with elevated ELR (OR = 2.02; p < 0.001) and EA-SIRI (OR = 2.19; p < 0.001). ROC curve analysis indicated modest discriminative power for identifying atherogenic dyslipidemia, with ELR and EA-SIRI yielding AUC of 0.60 (p < 0.001) and 0.62 (p < 0.001), respectively. Conclusions: Our findings suggest eosinophil-related inflammation contributes to immunometabolic dysregulation underlying dyslipidemia. ELR and EA-SIRI may offer insights into inflammation-driven lipid disturbances and help detect subclinical inflammatory activity associated with atherogenic lipid profiles. Full article

This study evaluated the effects of adding a Saccharomyces cerevisiae fermentation product (SCFP) to adult cat diets on palatability, intestinal health, nutrient digestibility, immune parameters, and the fecal microbiome over 42 days. Sixty-three healthy Domestic Short-hair cats were randomized to three diets: a control diet (CD) without SCFP, or the same diet containing 1.0% or 2.0% SCFP, targeting daily intakes of 150 or 300 mg/kg body weight, respectively. Body weight and blood parameters remained within reference ranges across all groups. Stool quality was largely not affected, although compared with controls, SCFP-supplemented cats had slightly firmer stools at day 21, and increased fecal pH. Shotgun metagenomic sequencing revealed that microbiome diversity remained steady in SCFP-fed cats, whereas diversity in the control group declined over time. Fecal immunoglobulin A concentrations were lower in cats supplemented with SCFP at 150 mg/kg BW by the end of the study, and positive shifts in the circulatory leukocyte profile were observed at both inclusion levels. Apparent total tract macronutrient digestibility did not differ among groups. Palatability tests showed diets with SCFP were generally preferred, indicating a potential benefit for commercial feline feeds, particularly at the 150 mg/kg BW level, which was preferred over 300 mg/kg BW. Overall, these findings suggest that SCFP can act as a functional ingredient in feline nutrition to maintain microbial diversity and enhance diet acceptance without compromising digestibility. Full article

Pancreatic ductal adenocarcinoma (PDA) exhibits diverse molecular aberrancies that contribute to its aggressive behaviour and poor patient survival. P-21-activated kinase 1 (PAK1) and PAK4 drive the tumorigenesis of PDA. However, their roles in tumour vasculature and the impact on immune response are unclear. This study aims to investigate the effects of PAK1 and PAK4 on tumour vasculature, immune cell infiltration, and the connection between using PAK1-knockout (KO), PAK4 KO, and wild-type (WT) PDA cells in cell-based and mouse experiments. Tumour tissues isolated from a syngeneic mouse model were immuno-stained to determine the changes in tumour vasculature and immune cell infiltration/activation, followed by a proteomic study to assess biological processes involved. PAK1KO or PAK4KO suppressed tumour growth by reducing angiogenesis while enhancing vascular normalisation, enhanced the infiltration/activation of T-cells and dendritic cells associated with upregulation of ICAM-1 and VCAM-1 in the tumour microenvironment, and stimulated vascular immune crosstalk via an ICAM-1-mediated mechanism. This was supported by proteomic profiles indicating the regulation of endothelial cell and leukocyte trans-endothelial migration in PAK1- or PAK4-knockout tumours. In conclusion, PAK1KO or PAK4KO enhanced tumour vascular normalisation while reducing angiogenesis, stimulating immune cell infiltration and activation to suppress tumour growth. Full article

Genome-wide paternal uniparental isodisomy mosaicism (GWpUPIDM) is an extremely rare condition characterized by varying proportions of an androgenetic cell line across different tissues. It is primarily associated with severe congenital hyperinsulinism (CHI), Beckwith–Wiedemann syndrome (BWS) stigmata, a high risk (69–79%) of developing neoplasia and, in some cases, additional manifestations of multilocus paternal imprinting disorders (MPIDs). We herein report the first Mexican/Latin American female patient GWpUPIDM presenting with non-syndromic CHI requiring subtotal pancreatectomy and persistent but unexplained asymptomatic diffuse hepatopathy. When she was 8.5 years old, whole-exome sequencing (WES) in blood revealed an unexpectedly high (~92%) proportion of regions of homozygosity. DNA profiling confirmed a single haploid set of paternal chromosomes in both biparental and androgenetic cell lines, with varying proportions of the androgenetic lineage in leukocytes (84%), resected pancreas (74%), buccal cells (47%), and hair follicles (0.7%). Additional WES trio analysis using gDNA from the patient’s buccal cells and blood samples from both parents revealed an allelic frequency of ~75% for the paternally inherited variant NM_000158.4(GBE1):c.555+1G>T [ClinVar:632422; dbSNP:rs759707498]. At age 8.5, the patient exhibited no clinical features of BWS, MPIDs, or neoplasia. However, she presented persistent hepatic abnormalities that warrant further investigation to rule out an unmasked glycogen storage disease type IV (OMIM#232500). Our findings emphasize the critical need for early diagnosis of GWpUPIDM using SNP-based microarray or WES with further confirmation through DNA profiling in patients presenting with CHI, placental mesenchymal dysplasia, BWS stigmata, or other MPID-related conditions, including neoplasia, to facilitate timely cancer surveillance and management. Full article