Search Results (649)

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Organoids are self-organizing multicellular structures generated in vitro that recapitulate the micro-architecture and function of an organ. They are commonly derived from stem cells but can also emerge from pieces of proliferative tissues. Organoid technology has opened novel ways to model development and disease, but it is not without challenges. Computational models of organoids have been established to elucidate organoid growth and facilitate the optimization of organoid cultures. This article is a systematic review of in silico organoid models constructed at single-cell or subcellular resolution. PubMed, Scopus, and Web of Science were searched for original papers published in peer-reviewed journals before 26 September 2025, yielding 439 records after deduplication. Two independent reviewers screened their titles and abstracts, retrieved 84 papers for full-text scrutiny, and identified 32 papers that met the inclusion criteria. They were grouped by organoid type: 12 intestinal, 1 airway, 2 pancreas, 3 neural, 1 kidney, 1 inner cell mass, 9 tumor, and 3 generic. The analysis of these works revealed that computer simulations guided experimental work. Parsimonious computational models provided insights into diverse organoid behaviors, such as the rotation of airway organoids, size oscillations of pancreatic organoids, epithelial patterning of neural tube organoids, or nephron segment formation in kidney organoids. Generally, a deep understanding was achieved through combined in silico and in vitro investigations (e.g., optic cup morphogenesis). Recent research trends suggest that next-generation computational models of organoids may emerge from a more detailed understanding of the complex regulatory circuits that govern stem cell fate, and machine-learning-based, high-throughput imaging of organoids. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a multifaceted systemic condition, with the mechanisms linking intrahepatic lesions to systemic complications remaining a significant enigma in the field. This review posits that extracellular vesicles (EVs) serve as pivotal mediators facilitating communication between the liver and the entire organism. Within the hepatic environment, lipotoxic hepatocyte-derived EVs modulate macrophage populations and stellate cells, thereby promoting inflammatory and fibrotic processes. Systemically, the liver engages in bidirectional communication with adipose tissue, the intestinal tract, the cardiovascular system, and the pancreas via EVs, thus orchestrating metabolic homeostasis. Furthermore, we critically evaluate non-invasive diagnostic strategies and emerging therapies, including both natural and engineered EVs, based on EV-based interventions. We highlight the substantial potential and current challenges associated with achieving precision medicine in MASLD through targeted modulation of this specific communication network. Full article

Diseases of the pancreas—such as pancreatic ductal adenocarcinoma (PDAC) and pancreatitis—have long been a challenge to treat. The study of lymphatics within the pancreas can provide some additional insights and offer new therapeutic targets. Here, we explore the development of pancreatic lymphatics and their connections to the nervous system and individual disease states, as well as the potential for therapeutic interventions. Lymphangiogenesis pathways in PDAC, driven by VEGF-C and other mediators, have been extensively explored, but specific therapeutic interventions are lacking. Furthermore, due to the emergence of PDAC with pancreatitis, insights could improve treatment in both settings. The role of neuroimmune interactions and control, as in other organ sites, appears as critical to both lymphatic and immune processes. With a better understanding of the lymphatic environment within the pancreas, we can develop more effective treatments for patients. Full article

Background/Objectives: Acute Pancreatitis (AP) is an unpredictable inflammatory disease associated with high morbidity and significant mortality, particularly in severe forms. Early death is primarily linked to Systemic Inflammatory Response Syndrome (SIRS) and Multi-Organ Failure (MOF). The objective of this study was to identify objective clinical and laboratory predictors of early and one-year mortality in AP patients and to evaluate the prognostic accuracy of commonly used severity scoring systems. Methods: This prospective, observational study enrolled 50 adult patients admitted to the Intensive Care Unit (ICU) at the University Hospital Center Bežaniska Kosa. Patients with chronic pancreatitis, trauma-induced AP, or late presentation were excluded. Severity scores (APACHE II, BISAP, Ranson, Pancreas) and biomarkers (C-reactive protein, Procalcitonin) were collected at admission (0 h) and dynamically at 48 h, 72 h and day 7. Endpoints were early (in-hospital) and one-year mortality. Results: Overall mortality was 16% (n = 8). Mortality was significantly associated with sepsis/septic shock (p < 0.001), severe AP (p = 0.001), prolonged mechanical ventilation, and ICU stay. At admission, APACHE II (AUROC 0.813) and BISAP (AUROC 0.807) showed good accuracy. Reassessment at 48 h markedly improved prediction: APACHE II achieved excellent value (AUROC 0.917), and the Ranson score became a strong predictor (p < 0.001). Procalcitonin (PCT) was identified as a significant and superior predictor of mortality from 48 h onwards (p < 0.001), outperforming CRP. One-year survival was significantly shorter among patients with sepsis, septic shock, severe AP, and prolonged ICU stay. Conclusions: Dynamic assessment using clinical scoring systems, particularly APACHE II and BISAP within the first 48 h, provides reliable mortality prediction in acute pancreatitis. The presence of sepsis, severe disease, and the need for prolonged organ support are key mortality determinants. Serial PCT monitoring offers sensitive, incremental value for risk stratification and guiding intensive care decisions in both short- and long-term outcomes. Full article

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β-cells. Both lymphocytes and various innate immune cells contribute to its immunopathogenesis. Among lymphocytes, in addition to CD8⁺ T cells, CD4⁺ T cells, and B cells, growing attention has been directed toward some unconventional T-cell subsets, such as TCRαβ⁺ double-negative T (DNT) cells, based on findings in several autoimmune/rheumatic diseases. This narrative review aims to summarize and analyze the available data on the potential role of DNT cells (and, in detail, the TCRαβ⁺ subset) in the immunopathogenesis of autoimmune diabetes/T1DM. Most of the current knowledge regarding DNT cell homeostasis in this pathological setting derives from experimental models, especially Non-Obese Diabetic (NOD) mice. In murine autoimmune diabetes, TCRαβ⁺DNT cells appear to exert a predominantly protective role against immune-mediated β-cell injury. These cells can be observed in multiple anatomical sites, including the thymus, peripheral blood, secondary lymphoid organs (spleen and lymph nodes) and, under pathological conditions, in non-lymphoid organs, like within the pancreas and, in detail, pancreatic islets, in the setting of autoimmune diabetes. Experimental evidence suggests that TCRαβ⁺DNT cells may attenuate the CD8⁺ T cell-mediated destruction of pancreatic β-cells, both directly and indirectly, through the inhibition of CD4⁺ T cells and B cells implicated in this immunopathological process. Unfortunately, very few studies have examined TCRαβ⁺DNT cells in patients with T1DM. This important knowledge gap highlights the need for dedicated clinical and translational research to better elucidate the role of TCRαβ⁺DNT cells in T1DM, especially given the preliminary findings pointing toward their potential immunoregulatory relevance. Full article

Clear cell renal cell carcinoma is the most common histological type of renal cancer, which is a common cancer type usually associated with a long clinical course. During this course, various metastatic sites can be observed. In this review, we have focused on metastases to the thyroid gland. We conducted research in three medical databases, including PubMed, Scopus, and Web of Science, using the same search algorithm. Our inclusion criteria focused on case reports and case series studies since 2011, covering therapeutic strategies for the primary and/or metastatic disease, as well as subsequent follow-up data. Studies with insufficient or uncertain data, or written in a language other than English, were excluded. An analysis of 510 articles from PubMed, 1729 from Scopus, and 649 from Web of Science, after application of inclusion and exclusion criteria, resulted in 77 reports, analyzing 189 patients. A description of the clinical, pathological, ancillary, and follow-up data, in the light of recent therapeutic schemes, was attempted. Our results suggest that metastases’ imaging features comprised more commonly a solitary nodule with a median size of 3.5 cm and worrisome features in ultrasonography, such as heterogeneity, hypoechogenicity, partially solid configuration, and variable internal vascularization. Histological and immunohistochemical examination of the lesion is necessary because these findings are not specific. Common non-thyroid metastases are seen in the urogenital system, lungs, and pancreas. We calculated the restricted mean survival from primary diagnosis at 274.6 months (95% CI: 264.3–285.0 months) and the restricted mean survival from thyroid metastases treatment at 93.9 months (95% CI: 65.3–122.4 months). Results regarding how patient characteristics affect these survival numbers were statistically nonsignificant (p > 0.05). Full article

Insulin resistance develops when skeletal muscle (SM), adipose tissue (AT), and the liver fail to respond adequately to insulin, a dysfunction closely intertwined with chronic low-grade inflammation. This combination leads to compensatory hyperinsulinemia, dysglycemia, and metabolic stress, driving major disorders such as type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease. Both adipokines and myokines are central modulators of this metabolic–inflammatory axis. In obesity, diabetes, MASLD, and thyroid dysfunction, alterations in myokines such as myostatin, irisin, fibroblast growth factor 21 (FGF-21), apelin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-15 (IL-15) influence glucose uptake, lipid oxidation, mitochondrial function, and systemic inflammation. Exercise-induced myokines exert insulin-sensitizing and anti-inflammatory effects, whereas myostatin and tumor necrosis factor-alpha (TNF-α) promote metabolic impairment. These pathways reveal extensive crosstalk between SM and key metabolic organs—including the liver, pancreas, AT, intestine, heart, and thyroid gland. In metabolic disease, inflammation-driven changes in deiodinase activity and triiodothyronine (T3) availability further link muscle dysfunction with thyroid imbalance. The aim of this narrative review was to elucidate the complex interplay between myokines, adipokines, inflammation, and insulin resistance, and to clarify their clinical relevance in metabolic and thyroid disorders. Given this integrative role of SM, sarcopenia should be recognized as a clinical marker of metabolic or thyroid dysregulation, and preserving muscle mass through structured physical activity should be a core therapeutic target. Full article

Although single-cell analyses have advanced our understanding of pancreatic ductal adenocarcinoma (PDAC), most studies to date have focused on primary and metastatic tumors. Here, we map cell composition, phenotypic plasticity, and microenvironmental remodeling from human normal pancreas through preneoplastic lesions to PDAC, with the preneoplastic phase recognized as a critical window for carcinogenesis. We pinpoint genes that are persistently dysregulated throughout malignant transformation and are associated with a poor prognosis. Focusing on ductal and acinar cells as the principal origins of PDAC, we delineate malignant preneoplastic cell clusters that exhibit strong carcinogenic potential. Immune profiling reveals marked expansion and functional reprogramming of macrophages during disease progression. Integrative analysis with human PDAC bulk transcriptomic cohorts identifies candidate compounds, such as Brefeldin A, with potential for intervention in preneoplastic disease. Together, our study elucidates dynamic molecular and cellular mechanisms underlying PDAC carcinogenesis and provides actionable insights for early intervention and targeted therapy. Full article

The prevalence of chronic diseases, including obesity and related endocrine disorders, has risen significantly in recent decades. As a result, there has been growing interest in fermented foods with probiotic properties, such as kefir, which have potential health benefits. This study aimed to evaluate the hepatoprotective and antioxidant effects of kefir milk (KM) in a high-fat diet (HFD)-induced obesity rat model, complemented by in silico molecular docking studies with antioxidant enzymes. Twenty-four adult rats were divided into four groups: control (1 mL/100 g bw semi-skimmed cow milk), KM (1 mL/100 g bw kefir milk), HFD (1 mL/100 g bw semi-skimmed cow milk + high-fat diet), and KM/HFD (1 mL/100 g bw kefir milk + high-fat diet). After 60 days of treatment, biochemical assays and histological examinations were performed to assess the effects on lipid profiles and organ health. Kefir milk demonstrated significant antioxidant activity, with increased total phenolic content and enhanced DPPH, ABTS, and FRAP radical scavenging activities compared to commercial milk. Furthermore, KM administration protected against liver metabolic disruptions (ALT, AST, and LDH) induced by the high-fat diet and reduced lipid peroxidation in liver and testis tissues. KM supplementation also increased the activity of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Additionally, KM improved the fatty acid composition and decreased the de novo lipogenesis (DNL) index, as well as enzyme activities (SCD and Elovl6) associated with the high-fat diet. Histological analysis of liver, pancreas, and heart tissues revealed that kefir milk attenuated structural damage caused by the high-fat diet, suggesting its protective role in oxidative stress regulation and organ function. These findings underscore the potential of kefir milk as a functional food for preventing metabolic disturbances and liver damage associated with obesity. Full article

Probiotics have been studied for their potential to treat chronic diseases. This study examined the use of Lacticaseibacillus rhamnosus BST.L-601 as an anti-diabetic symbiotic with sweet potato for fermentation. The medium supplemented with sweet potato showed increased productivity and enhanced storability. The anti-diabetic effect of fermented BST.L-601 was evaluated using the C2C12 myotube and a type 2 diabetes mellitus (T2DM)-induced db/db (Lepr^db/Lepr^db) mouse model. Treatment with heat-killed BST.L-601 increased glucose uptake by 125% and α-glucosidase inhibition in a dose-dependent manner without cytotoxicity for myotubes. 8 weeks of oral administration of BST.L-601 led to anti-diabetic activities in various biomarkers in the mouse model, including lowered fasting blood glucose by 88% and elevated mRNA expression of glucose metabolism-related factors IRS-1 (510%) and GLUT4 (181%) from skeletal muscle. Moreover, the improvement of induced T2DM in mice was supported by blood serum analysis. Immunohistochemistry showed increased insulin and decreased glucagon secreted from β and α cells in the pancreas islet. Microbiota analysis demonstrated elevated microbiome diversity in mice treated with BST.L-601. Furthermore, the safety and probiotic properties of the strain were confirmed. These results suggest that BST.L-601 fermented with sweet potato could be a functional symbiotic used to improve diabetes, particularly T2DM. Full article

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor, mainly affecting adolescents and young adults. While lung metastases are common, visceral metastases in the hepatopancreatobiliary system are extremely rare and usually associated with a poor prognosis. The limited diagnostic and therapeutic options for such metastases make the treatment of affected patients difficult. The possibility of very late metastatic onset in high-grade OS highlights the potential need for extended follow-up (FU) beyond established intervals. Methods: This study combines a retrospective analysis of prospectively collected data from the Vienna Bone and Soft Tissue Tumor Registry with a review of the literature of patients with OS and metastases to the hepatopancreatobiliary system. A descriptive statistical analysis is presented for the entire cohort. In addition, publications from scientific databases (PubMed, Embase) were analyzed to evaluate the frequency, diagnosis, therapy, and prognosis of visceral metastasis from both conventional OS and primary extraskeletal osteosarcoma (ESOS). Results: A total of six male patients with conventional OS and metastases in the liver (5) and pancreas (1), with a mean lesion size of 38 mm (range, 10–120), were included. The median age at the time of visceral metastasis was 29 years (mean, 32 years; range, 20–62 years), and the mean interval since initial diagnosis was five years and ten months (range, 9 months–10 years and 9 months). Visceral metastases are very rare in general and usually occur in advanced stages of disease. We identified 51 cases of visceral metastases from conventional OS and 34 cases of ESOS in the hepatopancreatobiliary system in the literature. The metastasis interval was three years (range, 15 months before diagnosis–17 years) at a median age of 27 years (mean, 32 years; range, 10–69 years). Conclusions: Visceral metastases from OS are rare but represent a significant therapeutic challenge. Early, targeted imaging in combination with improved methods for diagnosis confirmation and interdisciplinary treatment strategies may potentially improve the results. This study underlines the importance of early diagnosis and highlights the need for individualized long-term surveillance strategies exceeding ten years, especially in high-grade OS, aiming at early detection of late-onset metastasis. Full article

Background/Objectives: Developing and implementing clinical trials for rare diseases is complicated by the incomplete understanding of the varied genotype and subsequent phenotypic differences of a condition, particularly when low numbers of subjects are enrolled in a study. Moreover, a small-scale clinical study may indicate a positive outcome but have too small of a sampling population to adequately evaluate unwanted outcomes. Prader–Willi syndrome (PWS) is one such genetic disorder with varied subtypes and heterogeneity, where little progress has been made in treatment discoveries. Recently, the FDA approved diazoxide choline for treating key features of hyperphagia and obesity associated with PWS based on clinical trial experience. Diazoxide choline activates the ATP-sensitive potassium channel (KATP) of pancreatic beta cells, inhibiting the release of insulin. One of the subunits of KATP is the protein Kir6.2, the gene product of KCNJ11. Methods: Web-based programs and datasets were used to study the gene and protein functional enrichments of Kir6.2 and KCNJ11, including shared gene and/or protein–protein interactions, and biological processes and functions. Results: Four essential domains of related functions were identified: (1) apoptosis, protein degradation, and inflammation; (2) the coupling of G proteins needed for KATP channel activation; (3) glucose metabolism and control; and (4) the maintenance of intracellular ionic homeostasis. Conclusions: Cellular metabolism in the pancreas is linked to membrane excitability by KATP, which regulates insulin production, energy production and storage, appetite regulation, and fatty acid synthesis. As such, diazoxide choline may influence several biological systems beyond pancreatic and metabolic functions. Full article

Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which oxidative stress (OS) promotes pancreatic stellate cells activation and fibrosis. Ranunculus repens L. (R. repens) has been used in Algerian traditional medicine to treat conditions like hepatitis and diabetes. Galectins are β-galactoside-binding lectins implicated in several pathological processes, including inflammation. This study aimed to analyse the chemical composition and evaluate the protective effects of R. repens methanol extract (RRME) in an experimental CP model, as well as in cultured pancreatic cells. CP was induced by intraperitoneal injections of L-arginine in rats. The pancreas was examined histopathologically, using hematoxylin and eosin, and picrosirius red staining. OS markers were assessed in pancreatic homogenates, and RT-qPCR analysis was performed to evaluate the expression of fibrosis markers, proinflammatory cytokines, and galectins 4 and 9. The extract was characterized by Ultra-performance liquid chromatography mass spectrometry, and its antioxidant and antiapoptotic activities were evaluated in vitro using H₂O₂-induced intracellular reactive oxygen species (ROS) generation and paclitaxel-induced apoptosis in pancreatic cell lines. The results showed that treatment with RRME improved relative pancreatic weight and lowered serum lipase activities. It mitigated oxidative stress in pancreatic tissues and reduced fibrosis levels. Inflammation was attenuated, as indicated by decreased interleukin-6, tumor necrosis factor alpha, and leukocyte infiltration. Moreover, RRME down-regulated galectins 4 and 9. Finally, RRME attenuated ROS generation and apoptosis in vitro. These findings suggested that RRME may have therapeutic potential against CP by modulating OS and fibrosis. Full article

Type 2 diabetes mellitus (T2D) is a well-studied condition characterized by increased insulin resistance, β-cell dysfunction and amyloid deposition in the pancreatic islets. The condition is best understood in humans and veterinary species such as the domestic cat but is poorly described in zoo animals. A 16-year-old male binturong (Arctictis binturong) at Mandai Wildlife Reserve presenting initially for a left forelimb tremor was noted to have hyperglycemia (23.86 mmol/L; RI 2.93–18.94), with concurrent glucosuria, which persisted over 2 weeks. The animal was diagnosed with diabetes mellitus based on serial biochemical and urinalysis results and ultrasonography. No pharmaceutical treatment was instituted. Over 4 years the animal developed other age-related changes and was euthanized based on a declining quality of life. Postmortem investigation including histological examination found diffuse islet amyloidosis of the pancreas, consistent with T2D as seen in other species. To the authors’ knowledge, this is the first published case report of type 2 diabetes mellitus and pancreatic amyloidosis reported in the binturong. The popularity of the species in zoological institutions and long-term implications of the disease warrant further attention. Further research may be directed toward establishing diagnostic values in binturongs, as well as options for medical management. Full article