Search Results (1,292)

An adult female Eurasian otter (Lutra lutra), introduced with another subject in the National Park of Gran Paradiso (Aosta Valley Region, Italy), was found dead. The necropsy found a mass involving mainly the gallbladder walls with other multicentric masses in the liver and pancreas. In addition to these, through the histological examination, other nodules were detected in the pancreas, with structure similar to gallbladder neoplasm. Histopathology diagnosed it as neoplasia composed of epithelioid cells, forming lobules of tubules and pseudoacini, with a very low mitotic count, discrete cellular pleomorphism, and prominent fibrous stroma. Neoplastic cells demonstrated positive immunoreactivity for cytokeratin and negative immunoreactivity for S100. Gross and histologic lesions and immunohistochemical findings were consistent with a primary gallbladder carcinoma (GBC) of metastatic type. GBC is a rare neoplasm in both humans and animals, sometimes associated with cholelithiasis and cholecystitis, with few reports in the veterinary literature especially in cattle, pigs, dogs and cats. To the best of our knowledge, this is the first report of GBC in a Eurasian otter. Full article

Fenofibrate (FF), a lipid-lowering drug, may decrease the risk of cardiovascular diseases in some pathological settings, yet data on its cardiac effects in physiological aging is scarce. To determine FF and age effects on the heart’s morphology and expression of metabolism-related genes, we treated young and old male rats for 30 days with 0.1% or 0.5% FF. FF did not affect serum activities of LDH and creatine kinase in both age groups. Upon FF treatment the structure of the heart muscle did not change in young rats; however, 0.5% FF increased the abundance of collagen fibers in old rats, and lipid accumulation in cardiomyocytes in young and old animals. FF increased immunoreactivity of the hypertrophy marker NPPA that was more pronounced in old than in young rats, while VEGFB immunoreactivity did not change. FF upregulated phospho-AMPK and PGC1α protein levels only in the cardiac muscle of old rats, while in both age groups it mildly increased the expression of selected fatty acid oxidation genes. We conclude that the cardiac muscle response to FF is dose-dependent and influenced by age. The observed negative impact of high-dose FF in the hearts of aged rats underscores the importance of dose optimization in the elderly. Full article

Ozone pollution is a significant public health problem due to its association with chronic diseases. This study examines the effects of repeated exposure to low doses of ozone on intestinal barrier function in rats. Seventy-two male Wistar rats were divided into six groups. The control group was exposed to normal air, while the ozone groups received a dose of 0.25 ppm for four hours daily for periods of 7, 15, 30, 60, and 90 days, respectively. After treatment, the duodenum, jejunum, and colon were removed and analyzed by biochemical assays, Western blot, immunohistochemistry, and histological techniques. The results indicated an increase in oxidized lipids and structural alterations in the duodenum and jejunum after 7 days of ozone exposure. The result showed changes in haptoglobin, IL-1β, and IL-6. In addition, increased immunoreactivity varied according to intestinal structure and the duration of ozone exposure in the duodenum, jejunum, and colon. In conclusion: Ozone exposure causes an increase in proinflammatory cytokines that leads to a loss of regulation of the immune response in the duodenum, jejunum, and colon of rats, as well as structural changes that alter the intestinal barrier and perpetuate a state of chronic inflammation characteristic of inflammatory bowel diseases. Full article

Background/Objectives: This study aimed to evaluate the diagnostic and prognostic utility of B7-H3 expression in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to examine its association with clinical outcomes. Methods: This retrospective study included 99 patients with histopathologically confirmed gliomas (42 LGGs and 57 HGGs). B7-H3 expression was assessed using immunohistochemistry and scored by immunoreactive score (IRS). Results: B7-H3 expression was significantly higher in HGG compared to LGG (p < 0.001). The total IRS (B7-H3 A × B) demonstrated strong discriminative power (AUC = 0.816). High B7-H3 expression independently predicted disease progression (OR = 4.9, 95% CI: 2.4–10.1; p < 0.001) and was associated with IDH wild-type status and elevated Ki-67 index. Patients with high B7-H3 had significantly shorter overall survival (median 6 months vs. 42 months) and progression-free survival (median 3 months vs. 25 months) (both p < 0.001). Cox regression confirmed high B7-H3 as an independent predictor of mortality (HR = 2.9, 95% CI: 1.7–4.7; p < 0.001) and progression (HR = 2.6, 95% CI: 1.6–4.2; p < 0.001). Conclusions: B7-H3 expression is a reliable biomarker for distinguishing HGG from LGG and is independently associated with worse survival outcomes. Its assessment may aid in glioma classification and prognostication. Full article

Immunoglobulin superfamily member 11 (IGSF11) has recently emerged as a critical immune checkpoint ligand that interacts with the V-domain immunoglobulin suppressor of T-cell activation (VISTA) receptor to inhibit T-cell activation and promote immune escape. Preclinical studies have demonstrated that targeting the IGSF11-VISTA axis effectively reverses immunosuppression by enhancing T-cell effector functions and increasing the secretion of prostimulatory cytokines such as IFN-γ. This immune modulation shifts the tumor microenvironment from an immune “cold” state, characterized by low immune infiltration and activity, to a more immunoreactive “hot” state that is more susceptible to immune-mediated destruction. Moreover, combining IGSF11 inhibition with established therapies such as anti-PD-1/PD-L1 improves treatment efficacy in various cancer models. In this review, we focus on the immunomodulatory functions of IGSF11, its role in combination immunotherapies, and preclinical evidence supporting its potential as a novel therapeutic target to overcome resistance and improve cancer immunotherapy outcomes. Full article

Similarly to the short-lived messenger nitric oxide (NO), the more stable carbon monoxide (CO) molecule can also activate soluble guanylyl cyclase (sGC) to increase cGMP levels. However, CO-induced cGMP production is much less efficient. Using an accessible invertebrate model, we dissect a potential interaction between the canonical NO/sGC/cGMP and CO signalling pathways during development. The embryonic midgut of locusts is innervated by neurons that migrate in four discrete chains on its outer surface. Transcellular diffusing NO stimulates enteric neuron migration via cGMP signalling. The application of an NO donor results in virtually all enteric neurons being cGMP-immunoreactive while CO increases cGMP production only in approximately 33% of the migrating neurons. Cellular CO release appears to act as a slow down signal for motility. We quantify how CO specifically increases the interneuronal distance during chain migration. Moreover, time-lapse microscopy shows that CO reduces the directionality of the migrating neurons. These findings support the function of NO and CO as antagonistic signals for the coordination of collective cell migration during the development of the enteric nervous system. These experiments and the resulting insights into basic scientific questions prove once more that locust embryos are not only preparations for basic research, but also relevant models for screening of drugs targeting NO and CO signalling pathways as well as for isolating compounds affecting neuronal motility in general. Full article

In this study, we evaluated the protective effects of combined melatonin and vitamin D3 treatment on ovarian reserve and tissue architecture in a cyclophosphamide-induced premature ovarian failure (POF) rat model. Forty-nine adult female rats were randomly assigned to seven groups, including intact control (group 1), single-agent control (groups 2 and 3), POF (group 4), and POF + treatment (groups 5, 6, and 7) groups. Cyclophosphamide exposure led to elevated FSH and LH levels, reduced estradiol and progesterone levels, extensive follicular atresia, stromal fibrosis, and the marked degeneration of the ovarian ultrastructure. Additionally, the expression levels of PTEN, FOXO3a, and AMH were significantly downregulated, while caspase-3 and TNF-α immunoreactivities were increased. Notably, co-treatment with melatonin and vitamin D3 preserved primordial and growing follicle populations, restored hormonal balance, reduced stromal fibrosis, and attenuated apoptosis and inflammation markers. These findings highlight the potential of combined melatonin and vitamin D3 therapy as a fertility-preserving strategy that functions by mitigating chemotherapy-induced ovarian injury through multi-pathway modulation. Full article

Objectives: The aim of this study was to investigate the effect of Rebaudioside A (RebA) on acetylcholinesterase (AChE) immunoreactivity in cortical neurons of the rat brain. RebA is a steviol glycoside commonly used in the production of sweeteners. Beyond its application as a food additive for diabetes management, steviol glycosides have been shown to influence memory and learning processes. Methods: RebA was administered to rats at two concentrations (1 mg/mL and 2 mg/mL of water) over both short-term (15 days) and long-term (45 days) periods. Indirect immunohistochemical peroxidase–antiperoxidase staining was performed on histological frontal sections of the brain cortex. Results: Acetylcholinesterase-positive neurons were analyzed both morphologically and morphometrically. The results of the experiment revealed no significant morphological changes in AChE-immunopositive neurons, indicating an absence of neurotoxic effects associated with the sweetener in these neurons. However, the analysis demonstrated a reduction in AChE immunoreactivity, particularly after 45 days of treatment. Conclusions: These preliminary findings demonstrates that RebA affects the immunoreactivity of neurons positive for AChE. Given the observed effects, further studies should be implemented to investigate the exact influence of this dietary supplement on the cholinergic nervous system. Full article

SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study aimed to investigate the expression of Angiotensin-converting enzyme 2 (ACE2), spike protein, and CD68+ markers in placental tissue to demonstrate a possible correlation with the level of systemic oxidative stress biomarkers in patients who were infected with SARS-CoV-2 during pregnancy. A prospective clinical cohort study was designed to investigate the presence of CD68+ macrophages, ACE2, and spike proteins in placental tissue using immunohistochemical methods and to compare these results with oxidative stress from our previous study. Spike and CD68+ macrophages’ immunoreactivity were more pronounced in the placental tissue of patients from the SARS-CoV-2 group. Placental tissue spike protein and CD68+ immunoreactivity correlate with maternal and fetal Thiobarbituric Acid Reactive (TBARS) levels. This study has confirmed that spike protein expression in placental tissue is associated with the newborn’s stay in intensive neonatal care. Therefore, immunoreactivity analysis for the Spike antigen is important in detecting newborns at risk of early neonatal complications. Full article

The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be a promising target for modulating these processes. Cannabinoid and cannabinoid-related receptors have been identified in the amygdala of rodents, carnivores, and humans, but not in horses. This study aimed to investigate the gene expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R), transient receptor potential vanilloid 1 (TRPV1), and peroxisome proliferator-activated receptor gamma (PPARγ) within the lateral nucleus of six equine amygdalae collected post mortem from an abattoir using quantitative real-time PCR, cellular distribution, and immunofluorescence. mRNA expression of CB1R and CB2R, but not TRPV1 or PPARγ, was detected. The percentage of immunoreactivity (IR) was calculated using ImageJ software. Cannabinoid receptor 1 immunoreactivity was absent in the somata but was strongly detected in the surrounding neuropil and varicosities and CB2R-IR was observed in the varicosities; TRPV1-IR showed moderate expression in the cytoplasm of somata and processes, while PPARγ-IR was weak-to-moderate in the neuronal nuclei. These findings demonstrate endocannabinoid system components in the equine amygdala and may support future studies on Cannabis spp. molecules acting on these receptors. Full article

Background/Objectives: The aim of this research is to analyze the effect of paclitaxel on endoplasmic reticulum (ER) stress in spermatogenic cells. Methods: In the study, spermatogonium (GC1) and spermatocyte (GC2) cell lines were used. The IC50 dose of paclitaxel was calculated using an MTT assay. Each cell line was separated into two different groups: control (GC1-C, GC2-C) and paclitaxel-treated (GC1-P, GC2-P). The control cells were incubated under standard culture conditions. The paclitaxel group cells were incubated in culture medium containing the paclitaxel IC50 dose for 24 h. After the experiments, all groups were stained with GRP78, p-PERK, and p-eIF2α antibodies using semi-quantitative immunocytochemistry. Results: Paclitaxel showed cytotoxicity. In the experimental model of the paclitaxel-treated cells, all the markers showed elevated levels of immunoreactivity, indicating ER stress. Conclusions: Paclitaxel administration triggered ER stress in spermatogenic cells. Studies of ER-related stress mechanisms in spermatogenic cells with further advanced molecular analyses will be important for therapeutic strategies. Full article

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

The habenula (Hb) of the epithalamus is formed of the medial (MHb) and lateral (LHb) parts. The improper functioning of the Hb may lead to depression and anxiety. The glutamate excitotoxicity is accompanied by astroglia reactivity and leads to the damage of nervous system structures. The aim of the study was to assess the influence of monosodium glutamate (MSG) administrated subcutaneously to rats in doses of 2 g/kg b.w. (I) and 4 g/kg b.w. (II), on astroglia in the MHb and LHb. Based on immunohistochemical reactions, the morphology, number of astrocytes immunoreactive for glial fibrillary acidic protein (GFAP-IR) and S100β protein (S100β-IR), and their surface area, perimeter, number and length of processes, and cytoplasmic-nuclear immunostaining intensity for the studied proteins were assessed. In the MHb of animals receiving MSG, especially at a high dose, hypertrophy and an increase in the number of GFAP-IR and S100β-IR cells were demonstrated. In the LHb, only hypertrophy of processes in S100β-positive glia was observed. The immunostaining intensity increased in GFAP-IR glia and decreased in S100β-IR cells only in animals from group I. The results revealed that astroglia respond to MSG depending on its dose and the Hb part. This different behavior of glia may indicate their different sensitivity and resistance to damaging factors. Full article

Since carbohydrate antigen 19-9 (CA 19-9) is a significant biomarker for the clinical diagnosis and treatment of pancreatic cancer, a sensitive sandwich-type immunosensor was proposed with an epoxy functionalized covalent organic framework (EP-COF_TTA-DHTA) as the antibody carrier and an electroactive COF_{TTA-2,6-NA(OH)2} as the signal amplification probe for the sensitive detection of CA 19-9. The flexible covalent linkage between the epoxy-functionalized EP-COF_TTA-DHTA and the antibodies was employed to improve the dynamics of the antigen–antibody interaction significantly. Meanwhile, AuNPs@COF_{TTA-2,6-NA(OH)2} with abundant electroactive sites enhanced the current response of the immunoreaction significantly. After optimizing the incubation time and concentration of the antibody, CA 19-9 was quantitatively detected by differential pulse voltammetry (DPV) based on the sensitive sandwich-type immunosensor with a low detection limit of 0.0003 U/mL and a wide linear range of 0.0009–100 U/mL. The electrochemical immunosensor exhibits high specificity, stability and repeatability, and it provides a feasible and efficient method for the pathologic analysis and treatment of tumor markers. Full article

The available literature data indicate that obestatin, a peptide derived from the preproghrelin precursor, may modulate neuroendocrine function, particularly in appetite regulation and somatotrophic/gonadotrophic pathways. This review synthesizes animal studies assessing the influence of obestatin on central neuroendocrine systems. Obestatin has been shown to affect the hypothalamic appetite-regulating center through neuropeptides such as neuropeptide Y and agouti-related peptide, yet findings remain inconsistent between species. In rodents, its effects on food intake and energy balance are inconclusive, whereas sheep models demonstrate significant alterations in orexigenic gene expression and peptide immunoreactivity. Regarding the somatotrophic axis, obestatin showed no significant effect on growth hormone (GH) secretion in rodents; however, in sheep, it modulated growth hormone-releasing hormone and somatostatin mRNA expression, elevated pituitary GH synthesis, and increased circulating GH levels. Studies involving the gonadotrophic axis demonstrated the presence of obestatin in Leydig and pituitary cells, with in vitro evidence suggesting its ability to modulate intracellular pathways implicated in gonadoliberin, luteinizing hormone, and follicle-stimulating hormone release. The collective findings discussed in this article indicate that obestatin interacts with multiple hypothalamic–pituitary axes, though its effects vary depending on species and experimental conditions. This review highlights the complexity of obestatin’s central actions and the need for further research to elucidate its functional relevance in neuroendocrine regulation. Full article