Search Results (2,084)

Indigenous chickens are raised in various rural areas in large quantities throughout Sudan. They must be transported over various distances to centralized slaughterhouses or for other purposes. In this study, we examined indigenous chicken farmers’ perceptions of chicken welfare during transportation. A total of 160 indigenous chickens (80 control + 80 transported with their owners) participated in this study. Our findings revealed that 69% and 88% of the farmers indicated that they were not knowledgeable about animal rights and animal welfare, respectively. The majority of the farmers (86%) reported that they were unaware of animal protection laws. Furthermore, the transported chickens showed a significantly long tonic immobility duration (p < 0.05) compared to the control chickens. Moreover, low pecking behavior was significant (p < 0.05) in transported chickens compared to control, particularly on day one of the experiment. In addition, the mean values of glucose, TWBCs, monocytes, basophils, eosinophils, H/L ratio, Hb, MCHC, and PLT were significantly higher (p < 0.05) in transported chickens compared to the controls. In addition, TNF-a, IL-1β, IL-2, IL-4, IFN-γ, IL-17, as well as ROS, MDA, cortisol, glucose, and total cholesterol were significantly higher (p < 0.05) in transportation chickens compared to control, while CAT, GSH, ATP, and SOD were significantly lower (p < 0.05) in transportation chickens compared to control. We conclude that the traditional transportation of indigenous Sudanese chickens affected their welfare, and this was associated with farmers’ low perceptions of chicken welfare, and stress-induced blood profile changes. Full article

In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood–brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor κB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer’s disease: reduced bone density exacerbates Alzheimer’s disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities. Full article

Background and Objectives: Acute normovolemic hemodilution (ANH) is commonly used to minimize perioperative blood loss and transfusion requirements. While it is considered safe, the molecular effects of ANH on vital organs remain unclear. Aquaporins (AQPs), the principal cellular water transporters, may play a role in tissue adaptation or injury under hemodilution stress. This study aimed to evaluate the impact of ANH on AQP1, AQP3, and AQP4 expression profiles and their association with apoptotic and inflammatory markers in the aorta, heart, kidney, and liver. Materials and Methods: Male Hannover–Sprague Dawley rats (6 months old) were assigned to control (no procedure), sham (anesthesia only), and hemodilution (anesthesia and ANH) groups. ANH was induced using balanced crystalloid infusion. Physiological parameters, blood gases, electrolytes, and metabolic profiles were monitored. At 24 h post-ANH, tissues were harvested for immunoblot analysis of AQPs, as well as apoptotic and inflammatory markers. Results: At 24 h post-ANH, changes in potassium, calcium, and glucose levels, decreased hematocrit, increased lactate, decreased pH, base excess, and PaCO₂ were detected, indicating mild metabolic acidosis due to tissue hypoxia and impaired oxygen delivery. Apoptotic and inflammatory responses were observed across all tissues, but AQP alterations were organ-specific. In the heart, AQP1 downregulation correlated inversely with NF-κB and TNF-α levels, while AQP3 upregulation positively correlated with apoptosis. The aorta showed the opposite pattern. In the kidney, AQP4 downregulation was strongly associated with apoptosis and inflammation. Furthermore, ANH selectively increased the AQP3 expression without affecting AQP1 or AQP4 in the liver. Conclusion: ANH induces differential aquaporin expression patterns in major organs, with tissue-specific associations with apoptosis and inflammation. These findings highlight a potential mechanistic role for AQPs, particularly AQP1 and AQP3, in modulating tissue response to hemodilution. These molecular adaptations may serve as early indicators of tissue stress, suggesting clinical relevance for perioperative fluid strategies. Full article

Brain tumors elicit complex neuropsychiatric disturbances that frequently occur prior to radiological detection and hinder differentiation from major psychiatric disorders. These syndromes stem from tumor-dependent metabolic reprogramming, neuroimmune activation, neurotransmitter dysregulation, and large-scale circuit disruption. Dinucleotide hypermethylation (e.g., IDH-mutant gliomas), through the accumulation of 2-hydroxyglutarate (2-HG), execute broad DNA and histone hypermethylation, hypermethylating serotonergic and glutamatergic pathways, and contributing to a treatment-resistant cognitive-affective syndrome. High-grade gliomas promote glutamate excitotoxicity via system Xc⁻ transporter upregulation that contributes to cognitive and affective instability. Cytokine cascades induced by tumors (e.g., IL-6, TNF-α, IFN-γ) lead to the breakdown of the blood–brain barrier (BBB), which is thought to amplify neuroinflammatory processes similar to those seen in schizophrenia spectrum disorders and autoimmune encephalopathies. Frontal gliomas present with apathy and disinhibition, and temporal tumors lead to hallucinations, emotional lability, and episodic memory dysfunction. Tumor-associated neuropsychiatric dysfunction, despite increasing recognition, is underdiagnosed and commonly misdiagnosed. This paper seeks to consolidate the mechanistic understanding of these syndromes, drawing on perspectives from neuroimaging, molecular oncology, neuroimmunology, and computational psychiatry. Novel approaches, including lesion-network mapping, exosomal biomarkers or AI-based predictive modeling, have projected early detection and precision-targeted interventions. In the context of the limitations of conventional psychotropic treatments, mechanistically informed therapies, including neuromodulation, neuroimmune-based interventions, and metabolic reprogramming, are essential to improving psychiatric and oncological outcomes. Paraneoplastic neuropsychiatric syndromes are not due to a secondary effect, rather, they are manifestations integral to the biology of a tumor, so they require a new paradigm in both diagnosis and treatment. And defining their molecular and circuit-level underpinnings will propel the next frontier of precision psychiatry in neuro-oncology, cementing the understanding that psychiatric dysfunction is a core influencer of survival, resilience, and quality of life. Full article

Species of the Ferula genus are known for their traditional medicinal applications against diverse illnesses. Our previous study was the first to suggest the cholinesterase inhibitory activity of Ferula persica L. However, the neuroprotective efficacy of therapeutic molecules is often limited by their ability to cross the blood–brain barrier (BBB) and reach the brain. In the present study, the BBB permeability of the main molecules present in the aerial parts and roots of F. persica L. extracted under optimum conditions was assessed using two well-established methods: the parallel artificial membrane permeability assay (PAMPA) and the HBMEC cell culture in vitro model. The results demonstrated a high permeability of several neuroprotective compounds, such as apigenin, diosmetin, and α-cyperone. Additionally, the neuroprotective potential of F. persica extracts was evaluated using SH-SY5Y neuron-like cells exposed to different insults, including oxidative stress (H₂O₂), excitotoxicity (L-glutamate), and Aβ1-42 peptide toxicity. However, none of the obtained extracts provided significant protection. This study highlights the importance of in vitro cell culture models for a better understanding of BBB permeability mechanisms and reports the tentative identification of newly formed sulfated metabolites derived from the metabolism of ferulic acid, apigenin, and diosmetin by HBMEC cells. Full article

Utilizing paste feed within a recirculating aquaculture system for eel cultivation may lead to various challenges, such as water quality degradation and, hence, transitioning to floating pellet type feed becomes essential. In this study, we aimed to investigate the impact of different feed types (paste and floating extruded pellet) and rearing systems (recirculating aquaculture and flow through system) on water quality, growth, blood chemistry, body composition, and expression levels of digestive enzymes in Japanese eels (Anguilla japonica). Throughout the experiment, notable variations were observed in total ammonia nitrogen and nitrite nitrogen levels, with higher concentrations in the recirculating aquaculture system (1.00 ± 0.64 and 0.757 ± 0.464 mg/L, respectively) than paste groups (0.859 ± 0.651 and 0.485 ± 0.502 mg/L, respectively). Significant differences were observed in weight gain and specific growth rates, with the pellet group (154 ± 10% and 1.50 ± 0.06%/day, respectively) exhibiting higher values than the paste group (135 ± 13% and 1.37 ± 0.09%/day, respectively). Blood parameters showed significant differences depending on the culture system, with generally higher values observed in the flow-through system, while no significant differences were observed between feed types. Whole-body composition exhibited variations attributed to feed intake, with notable differences in crude protein and crude fat content among the experimental groups. The expression levels of digestive enzymes and nutrient transporters were higher when the eels were fed pellet-type feed and reared in recirculating aquaculture system. The study findings indicate that pellet feed enhances water quality management in RAS, leading to improved eel growth. Given its lower environmental stress, pellet feed is preferable to paste feed for optimizing eel production in RAS. Full article

Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition. Full article

Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption in the proximal renal tubules. Variants in this gene, such as rs11568476 (V477M), have been shown to significantly impair transporter activity. This study aimed to investigate the presence of the rs11568476 polymorphism in SLC13A2 and its association with hypocitraturia in Turkish patients with calcium-containing kidney stones. To our knowledge, this is the first genetic study evaluating this polymorphism in a Turkish cohort. Materials and Methods: This prospective cross-sectional study included 90 patients diagnosed with calcium-containing kidney stones at Düzce University Faculty of Medicine, Department of Urology. Based on 24 h urinary citrate levels, patients were divided into two groups: normocitraturic (n = 38) and hypocitraturic (n = 52). Blood and 24 h urine samples were analyzed for biochemical parameters. The rs11568476 polymorphism in SLC13A2 was analyzed using Real-Time PCR. Results: There were no significant differences between the two groups in terms of age, gender, and most biochemical parameters. Serum uric acid levels were significantly higher in the hypocitraturic group (p = 0.002), whereas family history of stone disease was more prevalent in the normocitraturic group (p = 0.024). Genetic analysis revealed no polymorphism in the rs11568476 region; all patients exhibited the homozygous wild-type genotype (GG). Conclusions: No association was observed between the rs11568476 polymorphism and hypocitraturia in this cohort. The absence of the polymorphism suggests that this variant may be rare or absent in the Turkish population. These findings highlight the importance of investigating additional genetic and environmental contributors to hypocitraturia and nephrolithiasis through larger, multicenter studies. Full article

Background: To personalize the care for persons with smoking-related lung disease, a thorough understanding of its etiology is essential. The role of pulmonary vessels remains poorly understood. Living at high altitude provides a natural model to investigate the effects of low oxygen levels on pulmonary vessels. This study aims to evaluate the relationship between living at high altitudes and small pulmonary vein and artery volumes. We hypothesize that small vein and artery volumes were independently associated with living at high altitude. Methods: We quantified small pulmonary vein and artery dimensions (ᴓ < 1 mm) on computed tomography (CT) down to 0.2 mm in diameter and normalized the dimensions by body surface area. In 8931 current and former smokers participating in the COPDGene study, we used multivariate regression models corrected for clinical and technical confounders. Results: 1262 residents (14.1%) were defined as high-altitude residents (~1600 m, Denver, CO, USA). Compared to lower-altitude residents, the high-altitude residents had a higher age (62.0 ± 9.1 vs. 59.6 ± 9.0 years), more pack-years smoked (46.8 vs. 44.1) and a lower FEV₁% predicted (64.6 ± 32.4% vs. 76.8 ± 25.2%). Both mean small artery volume (4.09 ± 0.89 mL/m² vs. 3.85 ± 0.90 mL/m²) and mean small vein volume (2.96 ± 0.53 mL/m² vs. 2.67 ± 0.53 mL/m²) were higher in high-altitude residents. Multivariate linear regression showed that, in those without COPD, high-altitude residents have a higher small vein volume (0.129 mL/m², p < 0.001) and higher small artery volume (0.170 mL/m², p = 0.001) compared to lower-altitude residents. There was no significant association in residents with COPD. Conclusions: In current and former smokers without COPD, higher small pulmonary vein and artery volumes were associated with living at high altitude, independent of lung disease or technical CT parameters. A potential cause includes vascular remodeling due to an elevated need for blood oxygen transport, which becomes concealed when COPD develops. Full article

Red blood cells (RBCs) are uniquely vulnerable to oxidative stress due to their role in O₂ transport and their high content of heme iron and polyunsaturated fatty acids (PUFAs). Despite lacking nuclei and organelles, RBC homeostasis relies on a finely tuned redox system to preserve membrane integrity, cytoskeletal organization, and metabolic function. Impairment of this delicate balance results in a series of oxidative events that ultimately leads to the premature clearance of RBCs from the bloodstream. This review outlines the main oxidative mechanisms that affect RBC at different levels, such as membrane, cytoskeleton, and intracellular environment, with a focus on the molecular targets of reactive species. The role of major antioxidant systems in preventing or reversing redox damage will also be examined, revealing their multiple mechanisms of action ranging from direct ROS scavenging to the enhancement of endogenous antioxidant defense pathways. Redox regulatory mechanisms in RBCs are required to maintain membrane integrity, cytoskeletal organization, and metabolic function. Disruption of these processes causes several oxidative processes that trigger premature RBC removal. Cumulative evidence places oxidative stress at the core of RBC dysfunction in both physiological aging and pathological conditions, including diabetes, inflammatory conditions, and hemolytic disorders. Antioxidant-based strategies, rather than providing generalized protection, should aim to selectively target the specific molecular pathways affected in distinct clinical settings. Full article

Background/Objectives: Although essential for oxygen transport and DNA synthesis, excess iron is toxic and can damage organs such as the kidneys. Research has shown that iron overload induces kidney injury, and aging contributes to kidney dysfunction through functional and structural changes. The interaction between iron overload and aging remains poorly understood. Therefore, this study investigated their combined effects on renal microstructure and function using an iron-dextran-injected mouse model. Methods: Young and old mice were divided into control and iron overload groups, renal function was evaluated by serum creatinine and albuminuria, and urinary iron excretion was also measured to assess iron handling. The structural changes were assessed using histological analysis and electron microscopy. Results: Although the iron overload groups had similar blood iron levels, the old iron overload group exhibited significantly higher levels of albuminuria, urinary iron excretion, and serum creatinine compared with the young group. In the iron overload model, histological and ultrastructural analyses demonstrated iron accumulation in mesangial and endothelial cells, glomerular basement membrane thickening, and foot process widening, which were more pronounced in aged mice, suggesting that aging exacerbates iron-induced kidney injury. Conclusions: These findings demonstrate that aging increases susceptibility to iron-induced kidney injury, as shown by the accelerated glomerular injury observed in iron-overloaded aged mice. Therefore, elucidating the effects of aging on iron metabolism may contribute to identifying approaches for reducing age-associated renal injury. Full article

The sphingolipidoses Fabry disease, Gaucher disease and Acid sphingomyelinase deficiency (ASMD) are the three most common lysosomal storage diseases for which treatment is currently available. Timely diagnosis with estimation of the disease severity and possibilities of follow-up of patients, whether or not under therapy, is crucial for providing good care and for the prevention of possible lethal complications. With this research we provide an efficient and sensitive detection method; its implementation in clinical practice could optimize the diagnosis and follow-up of patients with Gaucher, Fabry and ASMD. This detection method on dried blood spots (DBS) was validated according to the international Clinical and Laboratory Standards Institute (CLSI) guidelines, looking at reproducibility, linearity, carry-over and lower limit of quantification. Analogously, validation and subsequent comparison of the method validation results using another matrix, the Capitainer blood sampling cards (Capitainers), was fulfilled. The results showed that this detection method is fully applicable clinically when using DBS as well as Capitainers. In addition, even additional improvements of some validation parameters were found when using the Capitainers. Twenty-six patient samples and fifteen healthy samples were analyzed for case finding control. All patient cases were detected without ambiguity. We present a high-resolution mass spectrometry method that provides an accurate analysis for targeted screening, aiming for improved/accelerated diagnosis when added in the diagnostic pathway and monitoring of Fabry, Gaucher and ASMD in DBS as well as in Capitainers, with the main advantages of a small volume of blood samples, guaranteeing stability and easy transportation from the collection site to the laboratory. Full article

Exosomes are membranous vesicles that play a crucial role as intercellular messengers. Cells secrete exosomes, which can be found in a variety of bodily fluids such as amniotic fluid, semen, breast milk, tears, saliva, urine, blood, bile, ascites, and cerebrospinal fluid. Exosomes have a distinct bilipid protein structure and can be as small as 30–150 nm in diameter. They may transport and exchange multiple cellular messenger cargoes across cells and are used as a non-invasive biomarker for various illnesses. Due to their unique features, exosomes are recognized as the most effective biomarkers for cancer and other disease detection. We give a review of the most current applications of exosomes derived from various sources in the prognosis and diagnosis of multiple diseases. This review also briefly examines the significance of exosomes and their applications in biomedical research, including the use of aptamers and antibody–antigen functionalized biosensors. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Iridoids are compounds recognized for their neuroprotective properties and their potential application in the treatment of neurodegenerative diseases. Geniposide (GP) and asperuloside (ASP) are iridoids that have demonstrated some biological activities. In this study, the potential neuroprotective effects of these iridoids were evaluated through in silico and in vivo assays, using Caenorhabditis elegans (C. elegans) strains CF1553 (sod-3::GFP), GA800 (cat::GFP), and CL2166 (gst-4::GFP). The results suggested that neither compound appears to have good passive permeability through the blood–brain barrier (BBB). However, an active transport mechanism involving the glucose transporter GLUT-1 may be present, as both compounds contain glucose in their molecular structure. In addition, they can inhibit the activity of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). GP at 1 and 2 mM reversed the H₂O₂-induced increase in sod-3 expression, while ASP at 1 and 2 mM reversed the increase in gst-4 expression. Worm survival was more adversely affected by higher concentrations of GP than ASP, although both similarly reduced acetylcholinesterase activity. These findings suggest that GP and ASP exhibit very low toxicity both in silico and in vivo in C. elegans, and positively modulate key enzymes involved in antioxidant pathways, highlighting their potential for neuroprotective applications. Full article