Search Results (131)

Background/Objectives: Microplastics (MPs) are emerging environmental contaminants with potential implications for human health. Experimental studies suggest that MPs accumulate in the liver and promote inflammatory and fibrotic changes, but evidence from human tissues remains limited. This study investigated the presence of suspected MP-like particles in post-mortem human liver tissue and their associations with clinical, biochemical, hematological and histopathological parameters. Methods: Post-mortem liver tissue samples were collected from 55 adults. Suspected MP-like particles were extracted using hydrogen peroxide digestion, filtration, Nile Red staining and image-based quantification. Histopathological evaluation assessed inflammation, fibrosis, necrosis and fatty liver degeneration. Polarized light microscopy was used as a supportive morphological assessment method. Statistical analyses included Mann–Whitney U tests, Fisher’s exact tests and Spearman correlation analysis. Results: Detectable hepatic suspected MP-like particles were identified in 9 of 55 individuals (16.4%). Individuals with detectable suspected MP-like particles had significantly lower alanine aminotransferase (ALT) levels and leukocyte counts. The hepatic suspected MP-like particle burden showed weak positive correlation with liver fibrosis and inflammation and weak inverse correlation with ALT levels and leukocyte count. Fisher’s exact test showed that liver fibrosis and liver inflammation were significantly associated with detectable hepatic suspected MP-like particles, with higher unadjusted odds observed in the corresponding 2 × 2 contingency tables. No statistically significant associations were found for liver necrosis or fatty liver degeneration. Conclusions: Detectable suspected MP-like particles were identified in post-mortem human liver tissues and were more closely associated with fibrotic and inflammatory histopathological changes than with routine biochemical abnormalities. Larger studies using standardized detection methods are needed to confirm these results. Full article

Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy. Full article

Anesthetic agents are widely used in aquaculture to facilitate handling, transport, surgery, vaccination, tagging, and other husbandry procedures. However, most previous reviews have primarily focused on induction time, recovery duration, and welfare outcomes, with comparatively limited emphasis on blood physiology as an indicator of systemic anesthetic safety. The present review synthesizes current evidence regarding hematological, hemato-biochemical, blood gas, and immunohematological alterations induced by major anesthetic classes in aquaculture species. Literature published between 2000 and 2026 was retrieved from Scopus, Web of Science, Google Scholar, PubMed, ScienceDirect, and Springer Nature databases, with approximately 150 studies included following structured screening. Available evidence indicates that anesthetic exposure frequently alters erythrocyte and leukocyte profiles, cortisol secretion, glucose and lactate metabolism, hepatic enzyme activity, electrolyte balance, acid–base regulation, and blood oxygen transport. Respiratory depression, hypercapnia, hypoxemia, and transient metabolic acidosis were recurrent consequences of deep anesthesia, particularly during prolonged exposure or unfavorable environmental conditions. Several anesthetics also modulated innate immune responses through alterations in complement activity, respiratory burst function, cytokine signaling, and leukocyte redistribution. Collectively, the review highlights blood physiology as an essential framework for evaluating anesthetic safety and improving welfare-oriented aquaculture practices. Full article

Sepsis, which affects 49 million people yearly, killing 11 million of them, is known to induce severe liver dysfunction. It is characterized by extensive metabolic reprogramming, resulting in acute metabolic loss of function and maladaptive repair that can prime the organ for fibrosis rather than functional regeneration. To understand how intercellular communication dictates these outcomes, we performed cell type-specific bulk RNA-sequencing on hepatocytes (HEP), hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KC), and CD45⁺ leukocytes (CD45) from mice following polymicrobial sepsis. Cell-cell communication analyses using CellChat and NicheNet revealed a clear reorganization of the hepatic environment. While HSCs remain largely quiescent during homeostasis, after sepsis, they become the liver’s central signaling hub and broadcast potent fibrogenic and chemotactic signals (e.g., Ccl7) to surrounding cells. This actively suppresses hepatocyte metabolic functions, promotes leukocyte infiltration, and may further initiate early fibrogenic priming. Our findings highlight HSCs as regulators during septic acute liver injury, revealing communication nodes that could be targeted to constrain fibrosis responses and promote normal functions and repair. Full article

Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams and offspring. PS-MPs accumulated in multiple tissues, including blood, indicating maternal-to-offspring transfer. Continuous exposure reduced litter size, induced hepatic oxidative stress, and increased IL-6 and TNF-α levels in a dose-dependent manner in both dams and offspring. In dams, PS-MPs also decreased red blood cell and platelet counts and altered leukocyte composition, with increased lymphocyte and decreased neutrophil percentages at the high dose. Untargeted serum metabolomics revealed distinct exposure-related metabolic profiles, including 18 putatively annotated signature metabolites and 26 differentially abundant metabolites. Bilirubin and presqualene diphosphate were exclusively detected in exposed animals, whereas metabolites associated with lipid oxidation and mitochondrial fatty acid β-oxidation were elevated after exposure. RT-qPCR further supported altered expression of genes involved in these pathways. Overall, PS-MPs disrupted hematological homeostasis and metabolic regulation, likely through hepatic lipid peroxidation and systemic inflammation, and serum bilirubin and presqualene diphosphate may serve as candidate biomarkers of exposure. Full article

Background: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin. Methods: The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29. Results: NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt’s NASH classification). All these parameters were significantly (p < 0.01) modulated by quercetin treatment. Additionally, a significant (p < 0.001) correlation between IL-1β and hepatic injury parameters was observed. Conclusions: These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects. Full article

Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile of inpatients with complicated AP and to eventually identify laboratory markers associated with risks of sepsis and AMR infections. Material and Methods: A retrospective observational analysis on 553 adult inpatients diagnosed with complicated AP between 2021 and 2025 was conducted in a tertiary center. Demographic, clinical, and biological parameters were analyzed, including inflammatory markers and renal and hepatic markers. Results: Group characteristics included a mean age of 63.82 ± 15.67 years, and 63% were female. At admission, inflammatory markers were raised, with leukocytosis (15.6 ± 5.8 × 10³/µL), neutrophilia (10.1 ± 4.7 × 10³/µL), and elevated C-reactive protein (CRP) (median 43.2 mg/dL). Coagulation activation was significant with elevated fibrinogen of 747 ± 145 mg/dL and D-dimer with a median level of 1249 ng/mL, of which 58% exceeded 1000 ng/mL. Mild to moderate renal impairment was frequently observed (creatinine 1.69 ± 0.76 mg/dL). In multivariate analysis, no biological parameter proved to be an independent predictor of AMR status among organisms. Discussion and Conclusions: Inpatients with complicated AP showed a pronounced inflammatory and procoagulant biological profile that did not vary between AMR pathogen and non-AMR pathogen infections. This suggests that the clinical value of biomarkers, such as leukocyte and neutrophile, CRP, D-dimer, fibrinogen, procalcitonin, urea, and creatinine, lies primarily in assessing disease severity rather than predicting antimicrobial resistance. The microbiological profile was dominated by Gram-negative pathogens, particularly Escherichia coli, although a heterogeneous spectrum of microorganisms was identified. Full article

Background/Objectives: This observational study investigated associations between human leukocyte antigen (HLA) polymorphisms and imaging-defined hepatic steatosis (non-alcoholic fatty liver disease—NAFLD) and liver fibrosis in patients with rheumatoid arthritis (RA). Methods: Steatosis was assessed by transient elastography (FibroScan) and defined as controlled attenuation parameter (CAP) ≥ 275 dB/m; fibrosis was defined as liver stiffness measurement ≥ 8 kPa. We tested 11 frequent HLA alleles (HLA-A*02, HLA-B*07, HLA-B*08, HLA-B*27, HLA-B*35, HLA-B*44, HLA-B*51, HLA-DRB1*11, HLA-DRB1*14, HLA-DRB1*15, and HLA-DRB1*16). Associations were evaluated using multivariable logistic regression (individual and omnibus models) adjusted for age, body mass index (BMI), triglycerides, and glucose. Results: A total of 176 patients with rheumatoid arthritis were enrolled. NAFLD/steatosis was present in 35.2% of patients (n = 62), and fibrosis in 10.8% (n = 19). No HLA allele was significantly associated with steatosis or fibrosis after correction for multiple testing. BMI and triglycerides were independently associated with steatosis (BMI OR 1.22, 95% CI 1.12–1.34; triglycerides OR 1.48, 95% CI 1.04–2.18). For fibrosis, HLA-DRB1*15 showed the strongest trend-level association (OR ~2.6–2.9) but did not remain significant after correcting for multiple testing. Conclusions: In this RA cohort, metabolic factors (particularly BMI and triglycerides) were the dominant predictors of CAP-defined steatosis. No robust association between the tested HLA markers and steatosis or fibrosis was identified. Trend-level signals—most notably HLA-DRB1*15 for fibrosis—should be considered hypothesis-generating and warrant replication in larger, adequately powered cohorts. Full article

Lacticaseibacillus rhamnosus CRL1505 enhances antiviral immunity at mucosal sites, but its capacity to modulate liver immune responses remains unclear. Therefore, this study evaluated whether this immunomodulatory bacterium protects against Toll-like receptor 3 (TLR3)-mediated acute hepatitis induced by poly(I:C), and whether this effect depends on mucosal adhesion. BALB/c mice received the wild-type CRL1505 strain or the Δmbf CRL1505 mutant lacking the mucus-binding factor gene prior to poly(I:C) challenge. Liver injury, serum transaminases, and hepatic expression of interferons (IFNs), antiviral factors, inflammatory mediators, and regulatory cytokines were evaluated 48 h later. Poly(I:C) challenge induced acute hepatitis characterized by increased ALT/AST levels, leukocyte infiltration, and elevated hepatic IFNs and proinflammatory cytokines. The CRL1505 strain administration significantly reduced TNF-α, IL-1β, and IL-6 while enhancing IFNs, antiviral factors, and the regulatory cytokines IL-10 and IL-27, resulting in improved transaminase levels and attenuated liver damage. Notably, the Δmbf CRL1505 mutant conferred protection comparable to the wild-type strain. These findings demonstrate that L. rhamnosus CRL1505 exerts immunomodulatory and hepatoprotective effects during TLR3-driven hepatitis and that mbf-mediated adhesion is not required for this protection. Overall, CRL1505 emerges as a promising preventive strategy to enhance antiviral defenses and limit inflammation-associated liver injury. Full article

Kupffer cells (KCs) make up the predominant population of resident innate immune cells in the liver, serving as key immune sentinels that maintain local immune surveillance and immunoregulatory homeostasis. However, their functional involvement and phenotypic dynamics during radiation-induced liver damage (RILD) remain insufficiently explored. Therefore, we established a mouse model of RILD and, through systematic single-cell-level profiling of hepatic immune cell populations, found that KCs play a critical role in hepatic immune responses and undergo a pronounced radiation-induced shift toward a pro-inflammatory M1 phenotype. Further KC depletion/reconstitution, molecular assays, and coculture experiments consistently demonstrated that M1-polarized KCs exacerbate liver damage, with secretory leukocyte protease inhibitor (SLPI) being identified as a key molecular mediator driving this polarization and its pathogenic effects. To further substantiate these findings, we designed a liposome-based delivery strategy to selectively inhibit SLPI in KCs, which effectively suppressed M1 polarization and alleviated radiation-induced liver damage, underscoring the therapeutic relevance and translational potential of this approach in RILD. Overall, these findings demonstrate that radiation drives KCs toward an SLPI-dependent pro-inflammatory M1 state, thereby exacerbating liver injury. Moreover, targeted liposomal suppression of SLPI effectively reverses this polarization and protects against RILD, highlighting SLPI-modulated KC reprogramming as a promising therapeutic approach. Full article

Background: The human leukocyte antigen (HLA) is crucial for antigen presentation and vaccine efficacy. This study examined the association between HLA polymorphisms and the immune response to hepatitis B vaccination in children with acute lymphoblastic leukemia (ALL). Methods: 101 pediatric ALL patients at Shanghai Children’s Medical Center affiliated with Shanghai Jiaotong University School of Medicine who tested negative for hepatitis B surface antibody (anti-HBs) and were not infected with hepatitis B received three doses of the hepatitis B vaccine. Anti-HBs titers were measured before and after vaccination. Participants were divided into high- and low-response groups based on post-vaccination anti-HBs titers. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to genotype HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles. Results: Pre-vaccination anti-HBs titers were 3.38 ± 2.97 mIU/mL, and the post-vaccination seroconversion rate was 100% with mean titers of 429.61 ± 303.13 mIU/mL (p < 0.001). Following immunization, the low-response group (11.88%) had an anti-HBs titer of 56.47 ± 28.38 mIU/mL, while the high-response group (88.12%) had an anti-HBs titer of 479.93 ± 287.70 mIU/mL. There were significant differences in allele frequencies of B*3501 and Cw*0303 between the two response groups (p < 0.05). Binary logistic regression analysis showed that the B*3501 allele was negatively correlated with the anti-HBs response level (p < 0.05). Conclusions: HLA-B*3501 may be associated with lower antibody response levels in children with ALL who completed the full hepatitis B vaccination series. All these children demonstrated protection against the hepatitis B virus (HBV). We will subsequently validate the association between HLA-B*3501 and the level of hepatitis B vaccine immune response in children with ALL through expanding the sample size or conducting a multicenter study. Full article

The lipopolysaccharide (LPS)-induced inflammation model is widely used in mammalian studies but remains poorly investigated in a variety of fish species. We reproduce this model in rainbow trout, Oncorhynchus mykiss, a species of high economic value, to validate specific inflammatory biomarkers for reliably assessing the health and immune status of farmed fish. The inflammatory process, together with the effect of preconditioning, was modeled using two consecutive intraperitoneal injections of 300 and 600 µg LPS. We assessed innate immunity biomarkers, including the expression of inflammation-related genes (il1ß, il8), peripheral blood leukocyte profiles, serum bactericidal activity (SBA), and various serum and hepatic biochemical parameters. These parameters comprised the concentration of C-reactive protein (CRP, an acute phase protein), and the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase) measured at 24 and 96 h post-injection. In trout, LPS-induced effects involved the overexpression of pro-inflammatory interleukins (il1ß, il8), a left shift in white blood cells (characterized by a prevalence of immature neutrophils), and enhanced SBA. In contrast to warm-blooded animals, LPS challenge in trout did not appear to significantly elevate CRP levels or antioxidant enzyme activity. Further investigations in other fish species are needed to determine whether these are traits specific to trout or common to bony fish. Our findings provide a foundation for developing a biomarker panel suitable for the routine assessment of welfare, early detection of infection-associated inflammation in cultured fish, and the screening of the anti-inflammatory and immunostimulant activities of drugs and feed additives. Full article

Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which oxidative stress (OS) promotes pancreatic stellate cells activation and fibrosis. Ranunculus repens L. (R. repens) has been used in Algerian traditional medicine to treat conditions like hepatitis and diabetes. Galectins are β-galactoside-binding lectins implicated in several pathological processes, including inflammation. This study aimed to analyse the chemical composition and evaluate the protective effects of R. repens methanol extract (RRME) in an experimental CP model, as well as in cultured pancreatic cells. CP was induced by intraperitoneal injections of L-arginine in rats. The pancreas was examined histopathologically, using hematoxylin and eosin, and picrosirius red staining. OS markers were assessed in pancreatic homogenates, and RT-qPCR analysis was performed to evaluate the expression of fibrosis markers, proinflammatory cytokines, and galectins 4 and 9. The extract was characterized by Ultra-performance liquid chromatography mass spectrometry, and its antioxidant and antiapoptotic activities were evaluated in vitro using H₂O₂-induced intracellular reactive oxygen species (ROS) generation and paclitaxel-induced apoptosis in pancreatic cell lines. The results showed that treatment with RRME improved relative pancreatic weight and lowered serum lipase activities. It mitigated oxidative stress in pancreatic tissues and reduced fibrosis levels. Inflammation was attenuated, as indicated by decreased interleukin-6, tumor necrosis factor alpha, and leukocyte infiltration. Moreover, RRME down-regulated galectins 4 and 9. Finally, RRME attenuated ROS generation and apoptosis in vitro. These findings suggested that RRME may have therapeutic potential against CP by modulating OS and fibrosis. Full article

Background/Objectives: We evaluated whether fibrosis-4 (FIB-4) is associated with dynapenia and functional status in adults ≥65 years, and its value as a geriatric screening tool. Methods: In this cross-sectional study (July 2023–July 2025), 537 outpatients aged ≥65 years were evaluated. FIB-4 was calculated by the standard formula; a high-risk threshold of ≥2.0 was applied for age ≥65. Participants were compared as low- and high-FIB-4. Functional status was assessed by Basic Activities of Daily Living (ADLs), instrumental ADLs, and gait and balance tests. Dynapenia was defined as low muscle strength. Comorbidities, geriatric syndromes, and laboratory findings were recorded. Results: The high-FIB-4 group was older (78.6 ± 6.0 vs. 75.6 ± 5.8 years), had fewer women, and had lower BMI. POMA and instrumental ADLs scores were lower in the high-FIB-4 group, while basic ADLs and TUG duration did not differ significantly. Low grip strength was more frequent with high FIB-4. In sex-stratified analyses, FIB-4 correlated positively with age and aspartate transaminase (AST), and negatively with platelet count, leukocyte count, handgrip strength, POMA, and instrumental ADLs in women. In regression analysis low grip strength was associated with high FIB-4 score, but this relationship disappeared regardless of confounding factor in older female people. Lower BMI and higher leucocyte count is a risk factor for high FIB-4 score in the dynapenia group. Conclusions: FIB-4 reflects not only hepatic fibrosis risk but also geriatric vulnerability linked to dynapenia and functional decline in older adults. With age-adjusted cutoffs, FIB-4 may serve as a practical early-warning screen alongside nutritional and physical-performance assessments. Full article

This study evaluated the effectiveness of essential oil from Aloysia citrodora (EOAC) (48% citral and 19% limonene) for use in anesthesia and simulated transport of tambaqui (Colossoma macropomum) juveniles at two cargo densities (CDs). Concentrations of 0 (control), 10, 25, 50, 100, 150, 200, and 250 µL EOAC L⁻¹ were tested for use in anesthesia induction and recovery, while 0 (control) and 20 µL EOAC L⁻¹ were tested for their effects on the ventilatory rate (VR) and during 6 h simulated transport at a low CD (LCD, 65 g L⁻¹) and standard CD (SCD, 130 g L⁻¹). Fish were anesthetized at EOAC concentrations above 50 µL L⁻¹, with the optimal anesthesia (141.83 s) and recovery times (160.00 s) at 250 µL L⁻¹. The water unionized ammonia was lowest in the EOAC-LCD group. Using 20 µL EOAC L⁻¹ during transport minimized changes in the hematological parameters (erythrocytes, hemoglobin, hematocrit, total leukocytes, and heterophils) and reduced the liver aspartate aminotransferase activity at both CDs. Transport at an SCD, regardless of EOAC use, increased the plasma glucose, hepatic glycogen, and alanine transaminase activity. The VR was higher with 20 µL EOAC L⁻¹ than in the control group. In conclusion, our findings confirm that 20 µL EOAC L⁻¹ can effectively be used to transport tambaqui for up to 6 h without impairing fish health. Full article