Search Results (11,284)

Emodin exhibits promising hepatomodulatory potential, yet its precise actions remain poorly characterized across distinct hepatic pathological states. Dose-dependent effects of emodin (40, 80, and 120 mg/kg) were investigated in mice with metabolic dysfunction-associated steatotic liver disease (MASLD), as well as healthy control mice, through integrated histopathological, biochemical, metabolomic, and gut microbiota profiling. The 80 mg/kg dose tended to yield the most favorable hepatoprotective outcomes in MASLD mice, whereas the 120 mg/kg dose was accompanied by apparent adverse hepatic alterations in normal mice. Correlative analyses further suggested that such divergent hepatic responses may be potentially linked to the gut microbiota–short-chain fatty acid (SCFA) axis, as well as the modulation of BAX/Bcl-2 balance and ESR1 expression. The hepatic effects of emodin are state- and dose-dependent. The dose of 80 mg/kg may represent a plausible candidate therapeutic range for MASLD, and the gut–liver axis is proposed as a likely underlying regulatory pathway. Full article

Schistosomiasis (bilharzia) is a parasitic infection caused by trematodes of the Schistosoma genus and remains a significant health burden in endemic regions. Granulomatous host responses to deposited Schistosoma eggs in small veins and tissues result in progressive changes and characteristic imaging findings. This diagnostic radiological review synthesizes the published literature and highlights key and robust imaging findings that facilitate the diagnosis of Schistosoma mansoni and Schistosoma haematobium, with emphasis on modality-specific patterns and disease staging. Schistosoma mansoni primarily affects the liver, causing periportal fibrosis visible as “pipe-stem” echogenic thickening upon ultrasonography, which may progress to portal hypertension and chronic liver disease. Liver cirrhosis is the end-stage disease manifested as an irregular liver contour with surface nodularity and lobar redistribution as right lobe atrophy with left and/or caudate lobe hypertrophy. Schistosoma haematobium predominantly affects the genitourinary system, causing urinary bladder wall thickening and calcification. Early disease, within three months of infection, may present with fine calcification, firstly in the bladder base and then extending to the whole bladder and even to the ureters. Calcification appears as a line or two parallel lines on radiography and as a circle in axial CT images, which is pathognomonic for early-stage Schistosomiasis. In contrast studies, including conventional urography and CT urography, Schistosoma eggs appear as bubble-like filling defects in the ureter, kidney, and bladder, manifested as ureteritis, pyelitis, and cystitis cystica. Late stages appear as coarse calcification, fibrosis, strictures, and reduced bladder capacity and are associated with an increased risk of bladder squamous cell carcinoma. Moreover, Schistosomiasis calcification can present in genital organs, especially in the seminal vesicles; in the prostate in males; and in the vulva, cervix, and perineum in females. Ultimately, Schistosoma mansoni and haematobium eggs can reach the spinal cord, leading to acute myelopathy with paraparesis, urinary retention, or paraplegia. Recognition of characteristic imaging patterns of Schistosomiasis is essential for early diagnosis, accurate staging, and prevention of long-term complications. Full article

Tick-borne encephalitis virus (TBEV) is a major arthropod-borne flavivirus responsible for severe neurological disease in humans across Europe and Asia. It is maintained in nature through complex interactions within ticks and between tick vectors, vertebrate hosts and environmental factors. This review summarizes current knowledge on TBEV–tick interactions, focusing on virus acquisition, dissemination, vector competence, and long-term persistence within tick vectors. TBEV is acquired by ticks during blood feeding on viremic hosts or through co-feeding transmission under experimental conditions. Transovarial transmission has also been reported, as indicated by the detection of infected larvae in nature, although its efficiency appears to be low and variable. Following ingestion, TBEV infects and replicates in the tick midgut before dissemination via the hemolymph to secondary tissues, including the salivary glands and reproductive organs, which are essential for viral persistence and transmission. Vector competence and capacity vary between tick species and are shaped by intrinsic and extrinsic factors. Although transstadial transmission and transovarial transmission contribute to long-term virus maintenance, their efficiency is generally low and variable. In vitro models, including tick cell lines, have provided valuable insights into virus–tick interactions. Nevertheless, important knowledge gaps remain, particularly in understanding early events at the tick–host interface and mechanisms underlying viral dissemination and persistence within ticks. Full article

Efficient solubilization of nonpolar substances in polar solvents represents a fundamental challenge in environmental remediation, green chemistry, and separation processes. This limitation stems from the hydrophobic effect, which creates thermodynamic barriers, resulting in low intrinsic solubility and strong phase separation. This review examines the thermodynamic basis of solubilization, focusing on free-energy changes and molecular interaction mechanisms. It discusses various strategies, including surface and interface engineering, host–guest inclusion, solvent engineering, and nanostructure encapsulation, along with their practical applications. Future research directions include smart responsive materials, green solvent design theories, and precise construction of solubilization systems through multi-scale simulations. Full article

Bacillus velezensis-based probiotics are increasingly recognized for their potential to enhance intestinal health in companion animals, yet their mechanisms of action in canine epithelial systems remain incompletely defined. This study aimed to evaluate whether a live Bacillus velezensis probiotic consortia (BC) modulates epithelial barrier integrity, immune signaling, apoptosis-renewal pathways, and metabolic activity in canine-relevant intestinal and macrophage cell models. MCA-B1 proximal gastrointestinal epithelial cells and DH82 macrophage-like cells were exposed to BC cultures, followed by quantification of tight-junction expression, permeability (FITC-Dextran), cytokine responses, phagocytic activity, apoptosis-related markers, and metabolomic profiles. BC treatment significantly strengthened the epithelial barrier, inducing a marked upregulation of Claudin 1 (CLDN1) (11.3 fold), CLDN4 (2.4 fold), Occludin (OCLN, 1.7 fold), and increasing key proteins including ZO-2 and cingulin while reducing LPS-induced FITC-Dextran permeability to 94.5%. BC concurrently modulated innate immune signaling, increasing MyD88 (33.2%), IL-8 (14.6 fold), IL-18 (2.6 fold), and IFNB1 protein levels, while enhancing anti-inflammatory regulation, including a robust rise in DH82-derived IL-10. Apoptosis-renewal markers shifted toward physiological turnover, with increased BCL2 (1.9 fold) and reduced BAK1. Metabolomic profiling of BC activity revealed elevated AMP, abundant Peptide Transporter 1 (PEPT1)-transportable peptides, increased γ-glutamyl metabolites, and lower Glutathione disulfide (GSSG), consistent with AMPK-linked tight-junction assembly and glutathione-supported redox buffering. Together, these data indicate that Bacillus velezensis-derived metabolites positively influence barrier-related, immunological, and metabolic responses in a canine proximal intestinal epithelial system and modulate functional responses in macrophage-like cells. These in vitro findings contribute to the mechanistic understanding of host cellular responses to Bacillus-associated metabolites. Full article

Bovine mastitis is a major infectious disease in dairy cattle, causing significant economic losses and compromising animal health and milk quality worldwide. Among its etiological agents, Staphylococcus aureus is a key contagious pathogen due to its ability to establish persistent intramammary infections and evade host immune responses and antimicrobial therapy. This review summarizes current knowledge on the epidemiology, pathogenesis, clinical presentation, diagnosis, and control of S. aureus in bovine mastitis. Particular emphasis is placed on virulence mechanisms, including adhesion, intracellular persistence, biofilm formation, and immune evasion, which contribute to chronic and recurrent infections. The increasing prevalence of antimicrobial resistance, including methicillin-resistant and multidrug-resistant strains, is highlighted as a major challenge limiting treatment efficacy and posing risks within a One Health context. The review also discusses emerging alternative therapies and innovative control strategies, such as anti-biofilm approaches, immunomodulation, and improved diagnostics, aimed at reducing antimicrobial use. Advances in molecular and point-of-care diagnostic tools are considered for their role in early detection and targeted interventions. Overall, effective control of S. aureus mastitis requires integrated strategies combining prudent antimicrobial use, alternative therapies, improved hygiene, and a multidisciplinary One Health approach. Full article

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a biomarker of host immune competence. We assessed the association between baseline TTV DNA levels and immune responses to the Mpox virus (MPXV) and dengue virus (DGV) vaccines in two prospective cohorts. Methods: A total of 248 individuals were enrolled, and TTV DNA was quantified before vaccination. Humoral and cellular responses to MVA-BN (for MPXV) and QDENGA (for DGV) vaccines were measured by using serology, neutralization assays, and interferon-γ ELISpot, and correlations with TTV viremia were investigated. Results: TTV DNA was detected in 81.2% of individuals, with a significantly higher prevalence and viral loads in the Mpox-Vac group than in the DGV-Vac group. Between both groups, the only significant association observed was an inverse correlation between pre-vaccination TTV load and DGV neutralizing antibody titers in the DGV-Vac group and was limited to the subset of TTV-positive individuals; no additional correlations with antibody and T responses were identified. For the Mpox-Vac group, stratified analyses in people living with HIV (PLWH) confirmed this lack of association. Conclusions: TTV viremia does not predict vaccine immunogenicity in immunocompetent or mildly immunosuppressed individuals. These results, which derive from within-cohort analyses and do not rely on direct comparisons between heterogeneous vaccine populations, support the role of TTV as a marker of immune status along a continuum of immunosuppression, with predictive value likely confined to populations with more severe immune impairment. Full article

Silver Pomfret is increasingly threatened by many diseases under intensive artificial culturing conditions, yet conserved host biomarkers across different infections remain poorly defined. In this study, we integrated transcriptomic datasets from independent infections with Cryptocaryon irritans, Nocardia seriolae, and Photobacterium damselae subsp. damselae to identify shared host-response genes. By combining differential expression analysis with weighted gene co-expression network analysis, we prioritized six candidate genes associated with cross-pathogen infection responses. Random Forest and support vector machine analysis further supported their classification potential across the three infection models. Phylogenetic and structural analyses provided additional evidence for the conserved annotation of these proteins. GSVA-based signature analysis supported the cross-pathogen discriminatory capacity of the six-gene panel and suggested context-dependent contributions of individual genes across infection models. Immune signature analysis indicated distinct host immune response patterns under different pathogenic challenges, and candidate genes showed positive associations with inferred T cell-related signatures. Upstream regulatory prediction identified CTCF and the miR-17/20/93 family as potential regulators of these genes. Quantitative real-time PCR of the kidney further highlighted canx, rnd3, and angptl4 as the most robust infection-responsive candidates, with consistent temporal expression patterns observed from 0 to 24 h post-infection. These findings suggest a potential cross-pathogen host-response pattern in Silver Pomfret and provide preliminary support for future exploration of molecular markers for disease monitoring in aquaculture. Full article

Background/Objectives: The gut microbiome is a critical regulator of host metabolism, immunity, and the gut–brain axis. Exercise is a promising non-pharmacological modulator of microbial ecology, yet human evidence remains heterogeneous and the translational gap persists. This narrative review synthesizes mechanisms, human and animal evidence, and future directions for the exercise–gut microbiome axis. Methods: PubMed, Scopus, Web of Science, and SID were searched for articles published between January 2000 and February 2025. Keywords included exercise, physical activity, gut microbiome, gut microbiota, short-chain fatty acids, and gut–muscle axis. From 218 initial records, 89 original studies (47 human, 42 animal) met inclusion criteria and were critically appraised. Results: Exercise modulates the gut microbiome via splanchnic hypoperfusion, hyperthermia, altered transit time, and immune-mediated barrier regulation. Moderate-intensity continuous training consistently increases alpha diversity and enriches butyrate-producing taxa (Faecalibacterium prausnitzii, Roseburia hominis) and mucin-degrading Akkermansia muciniphila. High-intensity interval training transiently increases intestinal permeability in untrained individuals but, following adaptation, stimulates butyrate production via lactate cross-feeding metabolism—a recent breakthrough. Effects are transient and reversible upon detraining. Animal models establish causality through fecal microbiota transplantation; human randomized controlled trials demonstrate modest, intensity-dependent, and highly individualistic responses. Emerging evidence supports the gut–muscle axis in sarcopenia and personalized exercise prescription guided by microbiome profiling. Conclusion: Exercise shows promise as a low-cost modulator of the gut microbiome for enriching health-associated taxa and improving metabolic outcomes. Definitive evidence linking exercise-induced microbial shifts to enhanced athletic performance in humans remains lacking. Future research requires diet-controlled randomized controlled trials with ≥12-week interventions, shotgun metagenomics, and mechanistic validation of the gut–muscle axis in humans. Full article

In complex hydrogeological systems, such as multilayered aquifers in densely urbanized coastal areas, multi-parametric, multi-depth networks are required for discriminating between anthropogenic and natural signals. This study presents an evaluation protocol of a pre-existing piezometric network, composed of 66 piezometers, aimed at implementing a near real-time (NRTM) hydrogeochemical monitoring system in the Strait of Messina (Sicily, Italy) area. A rigorous selection process was conducted to determine the suitability of these sites for hosting permanent, above-ground instrumentation. After excluding 55 sites for logistical and administrative reasons, the remaining piezometers were evaluated through a multi-step protocol. Video inspections and vertical logs of temperature and electric conductivity were carried out to identify pipe integrity and screened sections. Water samples were collected, for the execution of geochemical and isotopic analyses, to distinguish between groundwater bodies and stagnant water or local infiltration. Finally, preliminary near real-time monitoring of water level and temperature assessed the response of the sites to hydrological cycles and tidal effects. A scoring system was applied to rank the sites, resulting in a priority list for the installation of the permanent monitoring network. The evaluation protocol was tested in the Strait of Messina, but it is based on a generical approach, independent of the specific setting of a study area, making it suitable for general applications worldwide. Full article

A within-host HIV dynamics model incorporating latent reservoirs, distributed time delays, and a B-cell-mediated humoral immune response is developed and analyzed mathematically. The model includes five compartments: uninfected CD4${}^{+}$ T cells, latently infected cells, actively infected cells, free virions, and B cells. Four distinct distributed delays are introduced to account for the periods between viral entry and the emergence of latently or actively infected cells, reactivation of latently infected cells, and intracellular virion production. For the non-delayed system, the basic reproduction number ${\mathcal{R}}_0$ is derived using the next-generation matrix method. Using Lyapunov functions and LaSalle’s Invariance Principle, a sharp threshold dynamic is proven: the infection-free equilibrium is globally asymptotically stable (GAS) when ${\mathcal{R}}_0\le 1$, whereas a unique endemic equilibrium is GAS when ${\mathcal{R}}_0>1$. For the full distributed-delay system, a delay-dependent reproduction number ${\mathcal{R}}_0^d$ is defined. The global asymptotic stability of the infection-free equilibrium is established for ${\mathcal{R}}_0^d\le 1$, and the global asymptotic stability of the endemic equilibrium is established for ${\mathcal{R}}_0^d>1$, using suitably constructed Lyapunov functionals that account for the delay history. Numerical simulations validate the analytical threshold behavior. A sensitivity analysis of ${\mathcal{R}}_0^d$ identifies the most influential parameters for potential intervention. A treatment-dependent reproduction number is derived, and the critical drug efficacy required for viral eradication is determined. The intracellular production delay is shown to act as a critical threshold for infection clearance. Full article

Microbiological culture and histology of deep tissue specimens are independent diagnostic criteria in fracture-related infection (FRI). However, the association between these tests has rarely been investigated, particularly in relation to clinical outcome after treatment. Patients undergoing surgery for International Consensus-confirmed FRI were included. All had ≥5 tissue specimens taken for microbiological culture and 2–3 for histology. The correlation between cultured pathogen, histological positivity (defined as ≥5 polymorphonuclear neutrophils/high power field), and outcome at one year after surgery was explored. FRI was confirmed in 430 patients, predominantly in the tibia (194), femur (111), upper limb (70), and ankle (40). A total of 321 (74.7%) were culture-positive and 334 (77.7%) were histology positive, while 265 (61.6%) were positive for both tests. Staphylococcus aureus was cultured in 169 (42.5%), coagulase-negative Staphylococci (CoNS) in 61 (15.3%), and Gram-negatives in 145 (36.3%) cases. Virulent microorganisms were strongly associated with positive histology (odds ratio 2.72; 95% CI 1.61–4.58) but not with clinical failure (OR 1.08; 0.42–2.75). Isolation of S. aureus was significantly associated with positive histology compared to other microorganisms (OR 2.21; 1.27–3.87). Surgery succeeded in 390 (90.7%) patients. Treatment failure was weakly associated with positive microbiology alone (OR 2.03; 0.83–4.96) or positive histology alone (OR 2.13; 0.81–5.6). Combined positive culture and histology was strongly associated with clinical failure (OR 2.3; 1.06–4.96). There was no difference in outcome between virulent and non-virulent bacteria when histology was positive, but both had higher failure rates compared to patients with negative culture or histology. A pronounced inflammatory response, as seen in histology, is a feature of virulent bacterial FRI. However, the presence of virulent infection alone does not dictate clinical outcome without marked inflammation. This suggests that outcome is at least as much related to the host response as to the bacterium. When the pathological response is prominent, this may lead to tissue necrosis, further bacterial invasion of adjacent tissues, osteolysis and loss of fracture stability, contributing to treatment failure. This deserves further study to understand the mechanisms behind this interplay and clinical outcome. Full article

Ubiquitination is a key post-translational modification regulating cellular signaling and innate immunity, and its reversal by deubiquitinases (DUBs) represents a critical mechanism exploited by pathogens for immune evasion. While ovarian tumor (OTU) domain-containing DUBs are well characterized in viral systems, their roles in fungal pathogens remain largely unexplored. In this study, we investigated two putative OTU domain-containing proteins derived from the plant pathogenic fungi Melampsora larici-populina (MlpOTU, EGG09943.1) and Taphrina deformans (TdOTU, CCG84064.1). Recombinant MlpOTU and TdOTU proteins were successfully expressed and purified from E. coli and exhibited high solubility and proper folding. Functional analyses in HEK293T cells demonstrated that both proteins significantly reduce global ubiquitination levels, confirming their deubiquitinase activity in vivo. Despite this shared enzymatic function, the two proteins displayed markedly distinct effects on host immune gene expression. MlpOTU selectively suppressed key antiviral effectors, most notably MX1, suggesting a targeted immune evasion strategy. In contrast, TdOTU induced robust upregulation of multiple immune-related genes, including type I interferons, indicating a divergent role. Neither MlpOTU nor TdOTU triggered robust apoptosis, supporting their role as modulators of host signaling rather than cytotoxic effectors. Collectively, these findings provide the first functional evidence that fungal OTU domain-containing proteins act as active deubiquitinases and reveal distinct strategies by which plant pathogens may manipulate host immune responses. This study establishes fungal OTU domains as promising targets for antifungal intervention and broadens our understanding of cross-kingdom evasion mechanisms. Full article

Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the FANCA gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control. Full article

The mealworm beetle, Tenebrio molitor, is a coleopteran of importance for both immunological and biotechnological research, and it has even been considered as a potential nutraceutical. In recent years, the study of T. molitor has undergone significant development, including immune response, host–parasite interactions, and physiological approaches. However, to perform this type of study, one of the main obstacles is obtaining sufficient hemolymph and viable hemocytes. Thus, we developed a protocol for adult specimens that enables the collection of up to 300 μL of the hemolymph–anticoagulant buffer mixture per specimen, containing approximately 1.5 × 10⁵ hemocytes, with viability ranging from 85% to 90%. The technique involves a double mesothoracic puncture (DMP) and the use of a modified anticoagulant buffer that prevents hemolymph clotting, enabling continuous extravasation and ensuring high yields. Additionally, the hemocytes recovered with this protocol are intact and can be used for subsequent analysis. The hemolymph obtained using this protocol and its applications will help to better understand the processes involving hemolymph and its components in T. molitor, paving the way for further applications. Full article