Search Results (1,164)

The internal organs of sea cucumbers (SCV) are a byproduct of the seafood processing industry and hold untapped potential as a functional food. This study investigates the antioxidant capacity of SCV and its regulatory effects on the gut microbiota in a mouse model of oxidative stress induced by chronic cold exposure. The results indicate that SCV possesses a rich nutritional composition, containing various components such as calcium, phosphorus, and polysaccharides, and exhibit strong scavenging activity against three types of free radicals in vitro: DPPH, OH⁻, and O₂⁻. SCV significantly reduced MDA levels in both serum and liver, while activating the Keap1-Nrf2/HO-1 pathway, leading to a significant decrease in the expression of HSP70 and HSP90 genes and a marked increase in Nrf2 gene expression, thereby alleviating oxidative damage. Histological analysis revealed that SCV alleviated liver damage, reducing hepatocellular vacuolization and inflammatory cell infiltration. Additionally, SCV modulated the diversity of the gut microbiota, increasing the abundance of Allobaculum, Turicibacter, Bifidobacterium, and Akkermansia, while enriching the synthesis pathway of vitamin B12 (PWY-7377). This study is the first to repurpose sea cucumber viscera waste into a functional food, demonstrating its dual mechanism of alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 antioxidant pathway and regulating the gut microbiota. These findings offer an innovative strategy for the high-value utilization of agricultural by-products and the development of multifunctional health-promoting products. Full article

Enterovirus D68 (EV-D68) is a significant global pathogen associated with severe respiratory infections and acute flaccid myelitis in children. Currently, there are no vaccines or antiviral drugs available for EV-D68, and a robust model to elucidate the pathogenesis of EV-D68 and evaluate treatment methods is lacking. We developed a mouse-adapted EV-D68 strain that caused progressive limb paralysis after intramuscular inoculation in 7-day-old mice. Viral load analysis showed that the skeletal muscle and spinal cord had the highest titers and most severe injuries. RNA sequencing of the infected muscle, brain, spinal cord, and lung tissues revealed differentially expressed genes (DEGs) associated with viral infection and pathogenesis. DEGs were significantly enriched in various pathways associated with antiviral immunity, interferon responses, and cytokine signaling. In the spinal cord, DEGs highlighted mitochondrial dysfunction and oxidative stress as crucial contributors to neural damage. Flow cytometry analysis of spinal cord cells showed that EV-D68 activates the immune system, leading to systemic inflammation and significant increases in CD8⁺ and CD4⁺ T cells, but limited neutrophil and monocyte infiltration. This mouse model provides a valuable tool for studying EV-D68 pathogenesis and evaluating antiviral and vaccine efficacy, thereby advancing the understanding of its neuropathological mechanisms. Importance: We developed a novel mouse model of EV-D68 that provides a valuable tool for studying its pathogenesis and evaluating antiviral and vaccine efficacy, deepening the understanding of its neuropathological basis. Full article

Preeclampsia (PE) is characterized by maternal hypertension accompanied with multi-organ dysfunction, such as maternal hepatic and renal dysfunction. Abnormal placental conditions may play a key role in regulating maternal organ function by promoting systemic inflammation. This study aimed to test the hypothesis that placenta-derived secretions contribute to hepatic and renal injury through interorgan communication using a PE-like mouse model. Pregnant mice were infused with angiotensin II (Ang II) from gestational day (GD) 12 (GD1 defined as the day of plug detection). Ang II infusion induced maternal hypertension, as well as liver injury (elevated serum amyloid A [SAA] secretion and alanine aminotransferase levels) and kidney injury (tubular damage with KIM-1 protein expression and immune cell infiltration). Treatment with placental-conditioned medium (CM) from Ang II-infused mice, but not from the control mice, stimulated SAA expression in liver cells. On the other hand, the effects of placental-CM from both the control and Ang II groups on kidney tubular cells were comparable. These findings suggest that placenta-derived secretions in the Ang II-induced PE-like phenotype specifically promote excessive SAA production in the liver. Furthermore, SAA administration in pregnant mice did not cause tubular injury but did promote renal immune cell infiltration, indicating that elevated hepatic SAA levels may contribute to maternal kidney inflammation. Taken together, these results suggest the presence of an in vivo organ network involving the placenta, liver, and kidneys during pregnancy, where dysfunction in one organ may exacerbate the pathogenesis of PE. Full article

Skeletal muscle dysfunction is a major systemic manifestation of COPD that shapes symptoms, exercise tolerance and mortality. Current evidence can be integrated within a Damage–Regeneration–Remodeling framework linking mechanics and biology to clinical phenotypes. Pulmonary hyperinflation and chest wall geometry chronically load the diaphragm and other respiratory muscles in COPD, whereas inactivity and exacerbation-related disuse underload locomotor muscles. Across muscle compartments, oxidative/nitrosative stress, activation of proteolytic pathways, mitochondrial and endoplasmic reticulum stress, microvascular limitations, neuromuscular junction instability, and myosteatosis degrade muscle quality. The diaphragm adapts with a fast-to-slow fiber shift, greater oxidative capacity, and sarcomere foreshortening, improving endurance, whereas limb muscles show atrophy, a glycolytic shift, reduced oxidative enzymes, extracellular matrix accrual, and fat infiltration. Translational levers that address these mechanisms include: (I) Reduce damage: bronchodilation, lung-volume reduction, oxygen, non-invasive ventilation, early mobilization, pulmonary rehabilitation, neuromuscular stimulation, and corticosteroid stewardship; (II) Enable regeneration: progressive resistance plus high-intensity/heavy-load endurance training; adequate protein and vitamin-D intake, and endocrine correction; and (III) Steer remodeling: increase physical activity (with/without coaching/telecoaching), functional assessment and CT or MRI monitoring, inspiratory-muscle training, and phenotype-guided adjuncts in selected cases. This framework clarifies why lung deflation strategies benefit inspiratory mechanics, whereas limb recovery requires behavioral and metabolic interventions layered onto systemic optimization. Full article

Low-fishmeal feed is increasingly being adopted across the global aquaculture industry. This study evaluated dietary Clostridium butyricum and alanyl-glutamine (Ala-Gln) supplementation in juvenile triploid rainbow trout (Oncorhynchus mykiss) with a low-fishmeal diet. Four diets were tested: basal diet (SBM, 15% fishmeal and 21.6% soybean meal), SBM + 0.5% C. butyricum (CB), SBM + 1.0% Ala-Gln, and SBM + 0.5% C. butyricum + 1.0% Ala-Gln (CB-AG). Fish were fed in 500 L tanks in recirculating aquaculture systems for 8 weeks (62.52 ± 0.47 g). Each group comprised three tanks, with each tank housing 30 fish. Then 10 fish per tank were challenged with Aeromonas salmonicida. CB-AG showed significantly higher weight gain and specific growth rates than the SBM group (p < 0.05). Mortality was significantly lower in CB-AG and AG than in SBM after A. salmonicida challenge. Histomorphology revealed significant differences (p < 0.05) between CB-AG and SBM in muscularis thickness, villus width, and height. SBM sections showed inflammatory infiltration and border damage were attenuated in supplemented groups. Serum malondialdehyde (MDA) and dioxygenase (DAO) were significantly lower in CB-AG than SBM (p < 0.05), while serum and hepatic lysozyme (LZM) and hepatic superoxide dismutase (SOD) were higher. Digestive enzymes indicated significantly higher trypsin and lipase activities in CB-AG (p < 0.05). CB-AG upregulated intestinal tight junction proteins and PepT1 and downregulated pro-inflammatory mediators. Combined 0.5% C. butyricum and 1.0% Ala-Gln inclusion effectively preserved growth performance, antioxidant capacity, gut microbiome homeostasis, and intestinal health in rainbow trout on low-fishmeal diets. Full article

Helicobacter pylori is a gastric pathogen that induces chronic gastritis, which may progress to neutrophilic activity, glandular atrophy, intestinal metaplasia, and gastric carcinoma. The aim of this study was to evaluate H. pylori-induced tissue damage. A total of 602 gastric biopsy samples were collected, categorized, and analyzed using hematoxylin and eosin and Giemsa staining, followed by molecular confirmation through PCR targeting the species-specific 16S rRNA gene. H. pylori density and histopathological features were evaluated and graded according to the updated Sydney classification system. H. pylori was detected in 55% (n = 334) of cases, and the antrum (50.83%, p < 0.00001) was the predominant site. A slightly higher prevalence was observed in females, accounting for 56.9% compared to males at 43.1%, which was attributed to sociocultural exposure differences. Individuals aged 11–40 years accounted for 58.3% (n = 195), highlighting early-age acquisition of infection. H. pylori infection was significantly linked to moderate-to-severe inflammation (63.2%, p < 0.00001) and neutrophilic activity (53.3%, p < 0.00001). Intestinal metaplasia and atrophy were infrequent, present in 0.6% (95% CI, 0.02, p = 0.149) and 0.9% (95% CI, 0.05, p = 0.430) of individuals. H. pylori infection causes chronic inflammation and neutrophilic infiltration of the stomach mucosa. Early identification and histopathological examination are essential in assessing H. pylori-related gastric pathology. Full article

Contact dermatitis is a common inflammatory skin disorder triggered by exposure to allergens or irritants and characterized by erythema, swelling, and immune cell infiltration. In this study, we investigated the anti-inflammatory effects of exosome-like nanovesicles derived from Peucedanum japonicum Thunb. (PjELNs) using a 2,4,6-trinitrochlorobenzene (TNCB)-induced mouse model of contact dermatitis. Intraperitoneal administration of PjELNs markedly reduced ear swelling and histopathological damage and decreased infiltration of inflammatory immune cells, particularly neutrophils. Moreover, PjELNs downregulated the expression of key pro-inflammatory cytokines, including CXCL2 and IL-1β, in the affected tissue. These findings indicate that PjELNs alleviate contact dermatitis-associated inflammation and suggest their potential as a novel plant-derived therapeutic modality for inflammatory skin diseases. Full article

Environmental pollution, driven by industrialization, urbanization, and agricultural practices, has intensified global ecological degradation. Among the most concerning pollutants is PFOS, a synthetic compound known for its chemical stability, environmental persistence, and bioaccumulative potential. Widely utilised in industrial and consumer products, PFOS infiltrates ecosystems and food chains, posing substantial risks to human and animal health. Upon exposure, PFOS disrupts lipid metabolism, damages cellular membranes, and alters signaling pathways through partial metabolism by cytochrome P450 enzymes. Accumulating evidence links PFOS to oxidative stress, mitochondrial dysfunction, endocrine disruption, neurotoxicity, and immunotoxicity. Critically, PFOS contributes to the development and progression of prostate, breast, and ovarian cancers via mechanisms such as hormonal interference, chronic inflammation, and epigenetic modifications. Epidemiological studies further associate elevated PFOS serum levels with increased cancer risk, particularly in occupationally and environmentally exposed populations. This review brings together the latest knowledge on PFOS emissions, mechanistic toxicity, and cancer-causing potential, highlighting the urgent need for focused research and improved regulatory measures to safeguard public health. Full article

To investigate the bending performance and damage characteristics of segmental joints with double sealing gaskets in large-diameter shield tunnels under high water pressure, this study established a three-dimensional high-fidelity numerical model of the segment-joint system based on the Pearl River Estuary Tunnel project. A comprehensive analysis was conducted on the mechanical and deformation behavior of large-diameter shield tunnel segmental joints under combined compressive/flexural loading. The research systematically examined the evolving relationships between bending moments, vertical displacements, and joint opening at the double-sealed gasketed joints under varying axial compression conditions, thereby elucidating the phased characteristics of joint deformation. The results indicate that the deformation patterns of double-sealed gasketed segmental joints under compressive/flexural loading exhibit pronounced nonlinearity and stage-dependent features. Both positive and negative bending moment scenarios demonstrate four distinct failure phases. Under high-water-pressure conditions, structural damage initiation consistently occurs at waterproof sealing grooves and bolt holes, regardless of bending moment direction. As loading intensifies, cracks propagate symmetrically at 45° angles from the joint interface, generating extended fracture networks, which creates additional water infiltration pathways, significantly compromising the joint’s waterproofing integrity. Full article

Background: Effective regenerative therapeutics for acute and chronic wounds remain a critical unmet need in biomedicine. Objectives: This study aimed to develop novel collagen–cerium oxide nanoparticle hydrogels designed to enhance cellular metabolism, proliferation, and antioxidant/antimutagenic activity, accelerating wound regeneration in vivo. Methods: Collagen–nanocerium composites were synthesized by combining a collagen extract with cerium oxide nanoparticles at defined concentrations. In vitro assays using human fibroblasts identified two formulations that enhanced proliferation and metabolic activity by 42–50%. FTIR spectroscopy confirmed chemical interactions within the composite matrix. Toxicity, antioxidant, and antigenotoxic effects were evaluated using Escherichia coli MG1655 lux-biosensors to assess their general toxicity, antioxidant and pro-oxidant activities, and antigenotoxic and promutagenic effects. In vivo efficacy was tested in Wistar rats with full-thickness skin wounds. Treated groups were compared to untreated controls and Dexpanthenol-treated positive controls. On days 3, 7, and 14, healing was assessed clinically, histologically, and morphometrically. Results: Biosensor analysis demonstrated non-toxicity and antigenotoxic activity of the nanocomposites, reduced DNA damage by up to 45%, providing 31–49% protection against H₂O₂ and 15–23% against O₂⁻ radicals. The animal study results demonstrated significantly accelerated healing with both nanocomposites versus control and comparison groups, evidenced by improved tissue regeneration, reduced inflammation, and increased fibroblast infiltration. Conclusions: The developed hydrogels exhibit promising pharmacological profiles, including antioxidant, antimutagenic, anti-inflammatory, and pro-regenerative effects validated across in vitro and in vivo models. Full article

This case-based review examines the spectrum of leukemic ocular involvement, focusing on its prognostic implications. A rare case of relapsed acute myeloid leukemia (AML) in a 63-year-old man is presented, featuring simultaneous orbital proptosis, adnexal involvement, choroidal and retinal infiltration, and hemorrhagic changes affecting both the anterior and posterior segments. This constellation of findings, affecting multiple ocular structures concurrently, highlights the eye’s potential role as a sanctuary site for leukemic cells and underscores the diagnostic challenge of distinguishing direct infiltration from treatment-related or secondary vascular damage. This case, integrated with a literature review, emphasizes that multifocal ocular signs may serve as early indicators of leukemic relapse and reinforce the need for close collaboration between ophthalmologists and hematologists in guiding patient management. Full article

Background: Cerebral malaria (CM) is a severe and often fatal complication of Plasmodium falciparum infection that causes devastating brain injury largely through immune-mediated mechanisms. Pathogenic brain-infiltrating CD8⁺ T cells are key drivers of CM pathology, yet the intracellular signals enabling their harmful autoimmune-like activity remain poorly defined. Here, we identify protein kinase C θ (PKCθ), a central antigen receptor-signalling mediator, as a critical contributor to experimental cerebral malaria (ECM). Methods/Results: Using a PKCθ null allele mouse strain on a C57BL/6N background, we demonstrate that PKCθ deficiency significantly improves survival in Plasmodium berghei ANKA (PbA)-infected mice without altering parasite burdens in the blood or brain. Mechanistically, loss of PKCθ skews T cell differentiation towards central memory (Tcm) rather than effector memory (Tem) phenotypes, thereby reducing effector differentiation and sequestration of CD8⁺ T cells in the cerebral microvasculature. This prevents extensive neurovascular damage, preserves neural tissue integrity, and alleviates neurological signs and symptoms. Our findings provide genetic evidence that PKCθ drives CD8⁺ T cell-mediated brain injury in ECM. Conclusions: These results underscore the potential for repurposing clinically PKCθ inhibitors as host-targeted interventions to protect against cerebral injury and improve outcomes in patients with CM. Full article

Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD). However, its exact targets remain to be elucidated. In this study, we used a mouse intestinal organoid–macrophage co-culture model to investigate the anti-inflammatory effects and immune effects of BBR. Our findings demonstrated that lipopolysaccharide (LPS) induced more robust inflammatory responses and epithelium damage in the co-culture system compared to the organoid alone. BBR effectively attenuated inflammation and restored epithelial barrier integrity by suppressing M1 macrophage polarisation and infiltration, alongside upregulating the expression and organisation of tight junction protein zonula occludens-1 (ZO-1). RNA sequencing and proteomic analysis revealed that BBR disrupted organoid–macrophage interaction by inhibiting chemokine (e.g., C-X-C motif chemokine ligand 1 (CXCL1) and macrophage migration inhibitory factor (MIF)) release from epithelial cells, thereby reducing macrophage recruitment. Collectively, our study establishes the organoid–macrophage co-culture system as a more physiologically relevant model for studying epithelial–immune interactions and elucidates the multi-target mechanism of BBR, which concurrently modulates epithelial cells, macrophages, and their crosstalk. These findings lay the foundation for further exploration of the therapeutic potential of BBR in inflammatory bowel disease and the development of targeted therapies that regulate cell interactions. Full article

Patients undergoing thoracic surgery or intensive care are frequently exposed to high-voltage electric fields generated by medical devices; however, the duration-dependent effects of such exposure on lung tissue remain unclear. This study aimed to investigate the histopathological and immunoinflammatory effects of exposure to a uniform 10 kV/m electric field for varying durations using a rat model. Thirty-five adult female Wistar rats were randomly assigned to five groups (n = 7): control, and 1, 5, 15, and 30 min exposure groups. Lung tissues were analyzed histologically with hematoxylin and eosin staining, and the immunohistochemical expression of IL-1β, RANKL, and TNF-α was semi-quantitatively assessed. Histopathological examination revealed a duration-dependent increase in lung injury, with the 30 min group showing marked epithelial loss, mononuclear infiltration, edema, and vascular congestion (p < 0.001). The expression of IL-1β, RANKL, and TNF-α remained minimal in the 1–15 min groups but was significantly elevated in the 30 min group (p < 0.001). These findings suggest that prolonged exposure to high-voltage electric fields induces substantial pulmonary inflammation and tissue damage, indicating the presence of a threshold beyond which inflammatory pathways are abruptly activated. These results highlight the importance of establishing safety guidelines for electric field exposure in clinical settings. Full article

Landslides are a major natural hazard capable of causing severe damage to infrastructure, ecosystems, and human life. They result from complex interactions of geological, hydrological, and environmental factors, with soil properties playing a crucial role by influencing the mechanical behavior and moisture dynamics of slope materials that drive initiation and progression. In South Africa, few studies have examined soil influences on landslide susceptibility, and none have been conducted in the Eastern Cape Province. This study investigated the role of soil physical and chemical properties in landslide susceptibility by comparing profiles from landslide scars and stable sites in the Port St. Johns and Lusikisiki region. Samples from topsoil and subsoil horizons were analyzed for soil organic matter (SOM), cation exchange capacity (CEC), saturated hydraulic conductivity (Ksat), exchangeable sodium adsorption ratio (SARexc), and texture. Statistical analyses included the Shapiro–Wilk test to evaluate data normality. For inter-profile comparisons, Welch’s t-test was applied to normally distributed data, while the Mann–Whitney U test was used for non-normal distributions. Intra-profile differences across more than two groups were assessed using the Kruskal–Wallis test for the non-normally distributed data. Results showed that landslide-prone soils had higher SOM, CEC, and Ksat in topsoil, promoting moisture retention and rapid infiltration, which favor pore pressure build-up and slope failure. Non-landslide soils displayed higher sodium-related indices and finer textures, suggesting more uniform water retention and resilience. Vertical variation in landslide soils indicated hydraulic discontinuities, fostering perched saturation zones. Findings highlight landslide initiation as a product of interactions between hydromechanical gradients and chemical dynamics. Full article