Search Results (55)

The present study describes a rare and extreme case of prolonged survival in domestic sheep (Ovis aries) under severe natural conditions, designated as the “Monyak” case (March 2026, Eastern Rhodope Mountains, Bulgaria). A 90-day period of complete isolation involving two adult ewes and a subsequently born lamb on an inaccessible rocky ledge, with very limited access to sources of food or water, was documented. Clinical assessment performed immediately following rescue revealed profound dehydration and cachexia accompanied by multisystemic abnormalities suggestive of a prolonged catabolic state. Biochemical analysis demonstrated marked azotemia, characterized by elevated serum urea and creatinine concentrations, which may indicate reduced renal perfusion and intensified protein catabolism. Electrolyte disturbances, including hypernatremia and hyperchloremia, were compatible with severe dehydration and substantial disruption of water−electrolyte homeostasis. Furthermore, increased total serum protein concentration and hematocrit values were observed, consistent with pronounced hemoconcentration. The metabolic profile demonstrated alterations in glucose homeostasis together with enhanced ketogenesis, findings compatible with an adaptive metabolic response to sustained energy deprivation. Elevated serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), accompanied by increased cortisol concentrations, may reflect hepatocellular stress and activation of the hypothalamic–pituitary–adrenal (HPA) axis associated with chronic physiological stress. Hematological evaluation revealed neutrophilia and lymphopenia, constituting a leukocyte pattern compatible with a stress leukogram and suggestive of endogenous glucocorticoid stimulation. Morphological examination of peripheral blood smears demonstrated pronounced echinocytosis and increased relative cellular density secondary to plasma volume depletion associated with dehydration. Additionally, neutrophilic hypersegmentation was observed, consistent with chronic physiological stress and cellular exhaustion. Ethological assessment suggests that maternal behavior and instinctive maternal care played a pivotal role in ensuring neonatal survival under conditions of extreme resource scarcity and sustained environmental stress. In conclusion, the “Monyak” case provides a unique natural model for investigating the physiological, metabolic, and behavioral adaptive mechanisms of ruminants subjected to prolonged starvation, dehydration, and chronic stress. The findings contribute valuable insights to veterinary physiology, clinical pathophysiology, and ethology, with potential implications for understanding the limits of adaptive capacity and survival under extreme environmental conditions. Full article

Background. This rat study reveals a new point: the considerable impact of unilateral adrenalectomy, severe vascular and multiorgan failure, occlusion/occlusion-like syndrome, and the stable gastric pentadecapeptide BPC 157 therapy. Based on the recent Fourier transform infrared (FTIR) spectroscopy vascular disturbance studies, particularly those after unilateral adrenalectomy in rats, the noted cytoprotective vascular recovery effect of the BPC 157 therapy may be useful. Methods. In rats, unilateral adrenalectomy (at 15 min, 5 h, 24 h) leads to integrated gross and morphological changes, vascular alterations, oxidative stress parameters, molecular markers and occlusion/occlusion-like syndrome and BPC 157 as useful therapy (/kg ig) (10 µg, 10 ng). Results. Peripherally and centrally, counteraction includes the lesions (adrenal, brain, heart, lung, liver, kidney, gastrointestinal tract), organ hemorrhage, and thrombosis. Attenuated/eliminated were arrhythmias, intracranial (superior sagittal sinus), portal, caval hypertension, and aortic hypotension. Significant resolution occurred via activation of collateral pathways, the azygos vein (direct blood flow delivery), and the recovered peduncle of the inferior suprarenal artery and superior suprarenal vein. Virchow’s triad circumstances were reversed. Occlusion/occlusion-like syndrome was counteracted as a whole. Also, BPC 157 counteracted adrenal lesions (lipid depletion, congestion). There were higher cortisol values, but still very low, and a shift toward the left of the adrenal compensatory weight increase. For the indicative conclusion along with previous studies, mechanistically, BPC 157 therapy exhibits the NO-system modulation/oxidative stress balance, increases NO-level, counteracts oxidative stress (malondialdehyde (MDA)), upregulates NOS1–3, and VEGF-A expression. Conclusions. These effects of BPC 157 therapy and its easy applicability deserve further consideration. Full article

Omega-6 polyunsaturated fats (ω-6 PUFAs) are vital for many physiological functions, but their impact on cardiovascular disease (CVD) risk is controversial. Eryptosis alters blood viscosity by providing a procoagulant surface and leads to anemia, which is a recognized risk factor for CVD. This study examines the toxic mechanisms of adrenic acid (ADR), an ω-6 PUFA enriched in inflammatory and oxidative conditions, in red blood cells (RBCs). Purified RBCs were prepared from healthy volunteers and treated with 10–100 μM of ADR for 24 h at 37 °C under various physiological conditions. Eryptotic markers were studied through flow cytometry including Ca²⁺ (Fluo4/AM), loss of volume (forward scatter), phosphatidylserine (PS) exposure (annexin-V-FITC), and oxidative stress (H₂DCFDA). Moreover, hemolytic markers were measured by colorimetric methods, whereas cellular morphology was visualized using a scanning electron microscope. ADR led to significant Ca²⁺ elevation, cell shrinkage and schistocyte formation, PS externalization, hemolysis, and oxidative stress. While guanosine, heparin, and NSC 23766 prevented eryptosis and hemolysis, melatonin, ATP, adenine, and L-NAME only prevented eryptosis. Conversely, mannitol and urea exacerbated eryptosis, whereas caffeine, mannitol, and urea under Ca²⁺ deprivation and membrane potential dissipation aggravated hemolysis. ADR induces erythrocyte membrane injury and eryptosis through Ca²⁺ elevation, oxidative stress, and metabolic exhaustion subject to inhibition by the Rac1 GTPase/NOS/COX pathway. Altogether, these findings present a novel mechanistic link between lipid dysregulation and RBC dysfunction which may improve dietary strategies to prevent and manage CVD. Full article

Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, “Pius Brînzeu” Emergency County Hospital, Timișoara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO/ISUP grade, tumor necrosis, sarcomatoid and/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies. Full article

The adrenal glands are central regulators of endocrine function and stress physiology, yet detailed species-specific anatomical baselines remain limited in cetaceans. This study provides a comprehensive gross, histological, morphometric, and ultrastructural characterization of the adrenal glands in 55 short-beaked common dolphins (Delphinus delphis) examined postmortem in the Canary Islands. Adrenal glands were evaluated macroscopically and microscopically, and histological corticomedullary ratios were calculated from mid-transverse sections. Associations with body length, sexual maturity, and cause-of-death category were assessed statistically. Transmission electron microscopy was used to characterize cortical and medullary cellular ultrastructure. Adrenal weight showed a positive correlation with body length. The histological corticomedullary ratio showed no lateral asymmetry but differed significantly between sexually immature and mature individuals, indicating ontogenetic remodeling of adrenal architecture. In contrast, the corticomedullary ratio did not differ significantly between adult dolphins that died from acute events and those that died following more progressive pathological conditions. Ultrastructural analysis identified characteristic steroidogenic cortical cells and two distinct chromaffin cell populations in the medulla. These findings establish the first integrated anatomical baseline for the adrenal gland in Delphinus delphis, providing essential reference data for comparative anatomy, veterinary pathology, and the interpretation of endocrine-related findings in cetaceans. Full article

Adrenal washout CT (AWCT) is a well-established reference standard for differentiating adenomas from non-adenomas and has been widely adopted in clinical practice for over three decades. However, in recent years, studies have demonstrated the low specificity of these washout values in diagnosing adenomas, with the latest 2023 European Society of Endocrinology guidelines noting the low quality of evidence regarding the accuracy of these cutoff values. Phaeochromocytomas are recognised as the classic mimickers of adenomas on AWCT as they exceed conventional washout thresholds. However, radiologists should be familiar with other hypervascular lesions to avoid potential diagnostic pitfalls. These hypervascular entities can pose a diagnostic challenge to radiologists who rely too much on washout values and percentages. In this pictorial essay, a comprehensive range of hypervascular adrenal lesions are illustrated. Incorporating lesion morphology, ancillary features, biochemical markers and the presence of extra-adrenal disease are essential for an accurate diagnosis and for avoiding inappropriate management. Full article

Quantifying tissue, molecular, and structural integrity is essential for biobank development. However, current assessment methods either involve destructive testing that depletes valuable biospecimens or rely on manual evaluations, which are not scalable and lead to interindividual variation. To overcome these challenges, we present PathQC, a deep-learning framework that directly predicts the tissue RNA Integrity Number (RIN) and the extent of autolysis from hematoxylin and eosin (H & E)-stained whole-slide images of normal tissue biopsies. Advancing over prior QC methods focused on imaging quality control, PathQC provides sample-quality control through the direct quantification of molecular integrity (RIN) and structural degradation (autolysis). PathQC first extracts morphological features from the slide using a recently developed digital pathology foundation model (UNI), followed by a supervised model that learns to predict RNA Integrity Number and autolysis scores from these morphological features. PathQC is trained on and applied to the Genotype-Tissue Expression (GTEx) cohort, which comprises 25,306 non-diseased post-mortem samples across 29 tissues from 970 donors, when paired ground-truth RIN and autolysis scores were available. Here, PathQC predicted RIN with an average Pearson correlation of 0.47 and an autolysis score of 0.45, with notably high performance using adrenal gland tissue (R = 0.82) for RIN and colon tissue (R = 0.83) for autolysis. We provide a pan-tissue model for predicting RIN and autolysis scores for new slides from any tissue type (GitHub). Overall, PathQC enables a scalable assessment of tissue molecular and structural integrity from routine H & E images, enhancing biobank quality control and retrospective analyses across 29 tissues and multiple collection sites. Full article

Background: The human fetal adrenal gland is a unique endocrine organ with distinct morphology and functional dynamics, which is significantly different from the postnatal adrenal. Its rapid growth and vital steroidogenic role during gestation have positioned it as a key regulator of fetal development and pregnancy maintenance. Objectives: To provide a comprehensive overview of the morphogenesis, function, regulatory mechanisms, and clinical implications of the human fetal adrenal gland, highlighting recent advances in understanding its development and its role in prenatal and postnatal health outcomes. Methods: A systematic review was conducted, including original research articles focused on human fetuses or validated animal models, examining the genetic, molecular, and hormonal mechanisms underlying adrenal development and function. Studies were excluded if they were editorials, case reports, focused on adult adrenal physiology, had small sample sizes, or were non-English publications. Study quality was evaluated using PRISMA guidelines. Results: The fetal adrenal gland develops from both mesodermal and ectodermal origins, forming three primary zones: fetal, transitional, and definitive. Each zone has distinct functions and developmental pathways. The fetal zone, which predominates, is responsible for producing dehydroepiandrosterone sulfate, DHEA-S, which is crucial for placental estrogen synthesis. The adrenal gland undergoes rapid growth and functional maturation, regulated by ACTH, placental CRH, IGF, and the renin–angiotensin system. Disruption of adrenal function is associated with conditions such as preterm birth, adrenal hypoplasia, congenital adrenal hyperplasia, and intrauterine growth restriction. Emerging evidence suggests that fetal adrenal hormones may influence long-term health through fetal programming mechanisms. Conclusions: The fetal adrenal gland plays a critical and multifaceted role in fetal and placental development. This gland influences placental development via steroid precursors (DHEA-S → estrogen synthesis), while also being regulated by placental factors such as the corticotropin-releasing hormone. Understanding its complex structure–function relationships and regulatory networks is essential for predicting and managing prenatal and postnatal pathologies. Future research should focus on elucidating molecular mechanisms, improving diagnostic tools, and exploring long-term outcomes of altered fetal adrenal function. Full article

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article

This study investigates the adrenal gland structure and gene expression in Acomys cahirinus compared to Mus musculus, aiming to assess its relevance for human adrenal disease modeling. We identified a well-defined zona reticularis in Acomys, resembling the human adrenal cortex. Transcriptomic analysis revealed upregulation of key steroidogenic genes (Cyp17a1, Sult1e1, Hsd3b2, Defb18, Kiss1, H2-Ke6), with validation by qRT-PCR and CAGE-seq. The gene Nupl1 showed discordant results between RNA-seq and CAGE. Pathway analysis highlighted enrichment of steroidogenesis and adrenal metabolism. Notably, a GTEx-based comparison demonstrated that Acomys adrenal gene expression closely mirrors the expression in the human adrenal cortex, whereas Mus musculus samples diverged toward brain-specific signatures. These findings suggest that Acomys cahirinus represents a promising model for adrenal research, though further studies including single-cell transcriptomics and functional assays are warranted to fully establish its translational potential. Full article

The adrenal medulla and organs of Zuckerkandl consist of chromaffin cells that produce, store, and secrete catecholamines. In humans, the adrenal medulla is known to function throughout postnatal life, while the organs of Zuckerkandl degenerate by 2–3 years of postnatal life. Although the history of investigation of chromaffin cells goes back more than a century, little is known about the reciprocal organogenesis of the adrenal glands and organs of Zuckerkandl during human fetal development. In the current study, we compared these two organs using serial sectioning, routine histological staining, and immunohistochemical reactions in human embryos, prefetuses, and fetuses from 8 to 26 gestational weeks. In our study, we used antibodies for tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase, which are enzymes of catecholamine synthesis, β-III tubulin, and S100. We found two morphological cell types (large and small) in the developing ganglia, organs of Zuckerkandl, and adrenal medulla, and two migration patterns of large cells and small cells. The immunohistochemical characteristics of these cells were determined. We revealed that the number of small cells increased significantly at the ages from 16 to 21–22 gestational weeks, followed by a decrease at 22.5–26 gestational weeks. The presence of two large cell subpopulations was suggested—those that migrate primarily from organs of the Zuckerkandl region and those that differentiate later from the small cells. We also determined that 12 gestational weeks was the age of the first appearance of phenylethanolamine N-methyltransferase reactivity in developing chromaffin cells, temporally correlating with synaptogenesis events. This is important data in the light of the controversial glucocorticoid theory of phenylethanolamine N-methyltransferase induction in humans. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Adrenal glands are vital endocrine organs whose accurate segmentation on CT imaging presents significant challenges due to their small size and variable morphology. This study evaluates the efficacy of deep learning approaches for automatic adrenal gland segmentation from multiphase CT scans. We implemented three convolutional neural network architectures (U-Net, SegNet, and NablaNet) and assessed their performance on a dataset comprising 868 adrenal glands from contrast-enhanced abdominal CT scans. Performance was evaluated using the Dice similarity coefficient (DSC), alongside practical implementation metrics including training and deployment time. U-Net demonstrated superior segmentation performance (DSC: 0.630 ± 0.05 for right, 0.660 ± 0.06 for left adrenal glands) compared to NablaNet (DSC: 0.552 ± 0.08 for right, 0.550 ± 0.07 for left) and SegNet (DSC: 0.320 ± 0.10 for right, 0.335 ± 0.09 for left). While all models achieved high specificity, boundary delineation accuracy remained challenging. Our findings demonstrate the feasibility of deep learning-based adrenal gland segmentation while highlighting the persistent challenges in achieving the segmentation quality observed with larger abdominal organs. U-Net provides the optimal balance between accuracy and computational requirements, establishing a foundation for further refinement of AI-assisted adrenal imaging tools. Full article

Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic–pituitary–adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs). Male adult SDRs and SHRs were subjected to lateral fluid-percussion injury. Immediate seizures were video recorded, corticosterone (CS) was measured in blood plasma throughout the study, and hippocampal morphology assessed 3 months post-TBI. Acute and remote survival rates were significantly higher in the SHRs compared to the SDRs (overall mortality 0% and 58%, respectively). Immediate seizure duration predicted acute but not remote mortality. TBI did not affect blood CS in the SHRs, while the CS level was transiently elevated in the SDRs, predicting remote mortality. Neuronal cell loss in the polymorph layer of ipsilateral dentate gyrus was found in both the SDRs and SHRs, while thinning of hippocampal pyramidal and granular cell layers were strain- and area-specific. No remote effects of TBI on the density of astrocytes or microglia were revealed. SHRs possess a unique resilience to TBI as compared with normotensive SDRs. SHRs show shorter immediate seizures and reduced CS response to the injury, suggesting the development of long-term adaptative mechanisms associated with chronic hypertension. Though remote post-traumatic hippocampal damage in ipsilateral dentate gyrus is obvious in both SHRs and SDRs, the data imply that physiological adaptations to high blood pressure in SHRs may be protective, preventing TBI-induced mortality but not hippocampal neurodegeneration. Understanding the mechanisms of resilience to TBI may also help improve clinical recommendations for patients with hypertension. Limitation: since more than a half of the SDRs with prolonged immediate seizures or elevated CS 3 days after TBI have died, survivorship bias might hamper correct interpretation of the data. Full article

Adrenocortical cancer (ACC) is a rare malignant neoplasm originating from the adrenal cortex, presenting limited therapeutic options. An avenue for improving therapeutic efficacy may involve a deeper understanding of the role of adrenocortical stem/progenitor cells in the pathogenesis of this disease. Although existing data suggest stem/progenitor characteristics in certain cell populations within ACC, the challenge remains to identify adrenocortical stem cell markers directly involved in its carcinogenesis. In our study, we aimed to identify multipotency markers such as LGR5 and CD90 in various ACC types to confirm their presence and localization. The study included tumor tissue samples from 13 patients with ACC treated at the Endocrinology Research Centre (Moscow, Russia) between 2005 and 2023. We conducted immunohistochemical analyses to identify the aforementioned markers and examined the association between their expression and clinico-morphological parameters. Our pilot study results demonstrate the presence of LGR5- and CD90-positive tumor cells in all samples. Despite the small sample size, we observed statistically significant differences in disease-free survival based on the number of CD90-positive cells. These findings suggest a potential diagnostic, prognostic, and predictive value of cancer stem cell markers, underscoring the need for their further analysis in a larger cohort of patients with ACC. Full article