Search Results (131)

Background/Objectives: Challenges in normothermic machine perfusion (NMP) remain, particularly concerning the duration for which individual organs can be safely preserved. We hypothesize that optimal preservation can be achieved by perfusing organs together in a multivisceral block. Therefore, our aim was to establish a platform for ex situ multivisceral organ perfusion. Methods: Multivisceral grafts containing the liver, kidneys, pancreas, spleen, and intestine were obtained from Yorkshire pigs. Three generation (gen) set-ups were tested during the iterative design process, and minor changes were made throughout. Gen 1 (n = 4) used a custom-designed single perfusion circuit. Gen 2 (n = 3) employed a dual perfusion circuit. Gen 3 (n = 4) featured a single perfusion circuit with an optimized basin and reservoir. Grafts underwent NMP using an autologous blood-based perfusate, while hemostatic parameters and function were assessed. Results: Comparing Gen 1 versus Gen 3, the mean aortic flow improved (1.018 vs. 2.089 L), resistance decreased (0.224 vs. 0.038), urine output increased (51.90 vs. 271.3 mL), oxygen consumption rose (43.56 vs. 49.52 mL O₂/min), perfusate lactate levels dropped (10.44 vs. 3.10 mmol/L), and the pH became more physiological (7.27 vs. 7.30). Cellular injury trended lower in Gen 3. Histological evaluation demonstrated minimal differences in Gens 2 and 3. Conclusions: We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 h. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicated organ viability. Multivisceral perfusion may serve as a plat-form for long-term NMP. Full article

Artificial insemination (AI) is essential in intensive pig production, which significantly depends on semen quality from boars selected for health, genetics, and fertility. While AI aims to improve productivity, larger litters often result in smaller and less resistant piglets. Beyond fertility and genetic traits, boars also influence offspring health. This study investigated the relationship between sperm parameters of highly fertile boars and both reproductive outcomes and piglet physiological indicators. Multivariate analysis revealed significant paternal effects on blood markers reflecting organ function, including those of the pancreas, liver, and kidneys, as well as on glucose homeostasis, lipid metabolism, oxidative stress, protein and carbohydrate metabolism, muscle contraction, and neural signaling. Notably, sperm velocity was correlated with mitochondrial function, which is crucial for sperm motility, capacitation, DNA integrity, and embryo development—factors likely linked to healthier, more resilient offspring. Boars transmitting superior sperm velocity, erythropoiesis efficiency, and oxygen transport capacities produced piglets with better glucose regulation, growth, and resistance to neonatal hypoglycemia. These findings underscore the broader impact of sperm quality on offspring vitality and suggest that advanced sperm analysis could improve boar selection and enable more effective, health-oriented breeding strategies. Full article

Histological techniques are essential for studying small crustaceans’, such as Neocaridina shrimp, anatomy and physiology. However, their small size and rapid tissue autolysis present challenges for fixation and processing. This study aimed to optimize histological methods for Neocaridina shrimp by evaluating different protocols for fixation, decalcification, and enzymatic digestion. Shrimp were fixed using 10% neutral-buffered formalin (NBF) and Bouin’s or Davidson’s fluid with or without modifications such as trypsin digestion, decalcification, or abdomen removal. Tissue preservation, section quality, and staining properties were assessed. Davidson’s fluid consistently gave generally acceptable fixation results, with minimal autolysis and good tissue preservation. Trypsin digestion increased tissue damage and autolysis, particularly in the liver and pancreas. Decalcification improved the quality of the sections; however, it increased autolysis and resulted in less specific staining. The optimal protocol involved the removal of the abdomen, followed by fixation in Davidson’s fluid and decalcification, which resulted in rapid penetration of the fixative, minimal autolysis, and a beneficial effect on staining. This study highlights the importance of adapting histological methods to the specific characteristics of small crustaceans and provides a basis for future research on Neocaridina shrimp. Implementing these optimized techniques will improve the quality and reliability of histological analyses in crustacean research, deepening the understanding of their biology and facilitating their use as model organisms in various scientific fields. Full article

Birds exhibit naturally high blood glucose concentrations, a physiological trait that, unlike in mammals, does not lead to typical pathological consequences such as diabetes mellitus. This review explores the unique features of glucose metabolism in birds, with a particular focus on the anatomy and function of the avian pancreas, the roles of key hormones such as insulin and glucagon, as well as the distinctive mechanisms of glucose absorption and utilization. Evidence suggests a dominant role of glucagon over insulin, along with adaptations such as insulin resistance and antioxidant defenses, which may contribute to birds’ apparent resilience to hyperglycemia-related complications. Despite these adaptations, cases of diabetes mellitus have been reported, primarily as secondary to other pathologies, including pancreatitis, hemochromatosis, infections, and toxicities. Diagnosis remains challenging due to interspecies variability and the lack of standardized assays. Treatment, mainly via insulin therapy, has shown mixed outcomes, often limited by the underlying disease severity. This review highlights the need for species-specific diagnostic tools and a deeper investigation into the pathophysiology of glucose regulation in birds, aiming to improve clinical outcomes, develop standardized therapies, and ultimately broaden the perspectives of comparative endocrinology. Full article

Perinatal vitamin D (Vit. D) deficiency (VDD) disrupts the development of key tissues involved in metabolic regulation, including the endocrine pancreas, white adipose tissue, and skeletal muscle. Brown adipose tissue (BAT), essential for thermoregulation and energy homeostasis, may also be affected, but the impact of perinatal VDD on BAT physiology remains unclear. In this study, forty female Wistar rats were fed either a standard AIN93G diet (1000 IU Vit. D₃/kg; control group, CT) (n = 20) or a modified AIN93G diet lacking Vit. D (VDD group) (n = 20) for six weeks prior to conception and throughout gestation and lactation. Male offspring were evaluated at weaning (PN21) and adulthood (PN180) after Vit. D status was normalized through a standard diet. We found that perinatal VDD reduced total lipid droplet area, increased oxygen consumption, and upregulated thermogenic gene expression in BAT at weaning. Correspondingly, VDD offspring exhibited greater cold tolerance and enhanced BAT recruitment upon cold exposure (4 °C). Notably, normalization of Vit. D status by adulthood fully reversed these changes, indicating that while perinatal VDD transiently enhances BAT thermogenic activity during early life, it does not produce lasting effects into adulthood. Full article

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone associated with the regulation of biological rhythms. The indoleamine is secreted by the pineal gland during the night, following a circadian rhythm. The highest plasmatic levels are reached during the night, whereas the lowest levels are achieved during the day. In addition to the pineal gland, other organs and tissues also produce melatonin, like, for example, the retina, Harderian glands, gut, ovaries, testes, skin, leukocytes, or bone marrow. The list of organs is extensive, including the cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, carotid body, placenta, and endometrium. At all these locations, the availability of melatonin is intended for local use. Interestingly, a decline of the circadian amplitude of the melatonin secretion occurs in old subjects in comparison to that found in younger subjects. Moreover, genetic and environmental factors are the primary causes of diseases, and oxidative stress is a key contributor to most pathologies. Numerous studies exist that show interesting effects of melatonin in different models of disease. Impairment in its secretion might have deleterious consequences for cellular physiology. In this regard, melatonin is a natural compound that is a carrier of a not yet completely known potential that deserves consideration. Thus, melatonin has emerged as a helpful ally that could be considered as a guard with powerful tools to orchestrate homeostasis in the body, majorly based on its antioxidant effects. In this review, we provide an overview of the widespread actions of melatonin against diseases preferentially affecting the elderly. Full article

Type 2 Diabetes (T2D) is a complex metabolic disorder that affects multiple organs, leading to severe complications in the pancreas, kidneys, liver, and heart. Prolonged hyperglycemia, along with oxidative stress and chronic inflammation, plays a crucial role in accelerating tissue damage, significantly increasing the risk of diabetic complications such as nephropathy, hepatopathy, and cardiovascular disease. This review evaluates the protective effects of various antidiabetic treatments on organ tissues affected by T2D, based on findings from experimental animal models. Metformin, a first-line antidiabetic agent, has been widely recognized for its ability to reduce inflammation and oxidative stress, thereby mitigating diabetes-induced organ damage. Its protective role extends beyond glucose regulation, offering benefits such as improved mitochondrial function and reduced fibrosis in affected tissues. In addition to traditional therapies, new classes of antidiabetic drugs, including sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists not only improve glycemic control but also exhibit nephroprotective and cardioprotective properties by reducing glomerular hyperfiltration, oxidative stress, and inflammation. Similarly, GLP-1 receptor agonists have been associated with reduced hepatic steatosis and enhanced cardiovascular function. Preclinical studies suggest that tirzepatide, a dual GLP-1/gastric inhibitory polypeptide receptor agonist may offer superior metabolic benefits compared to conventional GLP-1 agonists by improving β-cell function, enhancing insulin sensitivity, and reducing fatty liver progression. Despite promising preclinical results, differences between animal models and human physiology pose a challenge. Further clinical research is needed to confirm these effects and refine treatment strategies. Future T2D management aims to go beyond glycemic control, emphasizing organ protection and long-term disease prevention. Full article

Type 2 diabetes mellites (T2DM) is the most common form of diabetes and affects a significant portion of the population. Obesity-related increases in free fatty acids and glucose in the diet contribute to β-cell dysfunction and loss, ultimately leading to the onset of T2DM. The endocannabinoid system, which is present throughout the body, plays a vital role in regulating various physiological processes, including those in the pancreas. This system has been implicated in metabolic disorders like obesity and diabetes, as it helps to regulate appetite, food intake, and fat production. Phytocannabinoids from Cannabis sativa have the potential to influence the endocannabinoid system, offering a promising therapeutic approach for diabetes and its complications. Using high-glucose–high-lipid (HGHL)-induced INS-1 β-cells, we investigated the protective effects of two major (THC and CBD) and three minor (THCV, CBC, and CBG) phytocannabinoids on high glucose–high lipid (HGHL)-induced apoptosis, cell cycle disruption, and impaired function of beta-cells. Our results showed that all five phytocannabinoids reduced HGHL-induced apoptosis, likely by decreasing TXNIP protein levels. Additionally, THC and all three minor phytocannabinoids provided protective effects against functional impairments caused by HGHL exposure. Full article

Background and Objectives: With physiological aging, the pancreas is expected to decrease in size as in every organ. The objective of this study was to examine the correlation between pancreas volume (PV), nutritional status, and glycolyzed hemoglobin A1c (HbA1c) in elderly patients with and without type 2 diabetes mellitus (DM). Materials and Methods: Between July 2020 and April 2022, 109 patients aged ≥ 65 years who applied to geriatrics clinics and outpatient clinics were included in the study. PV was measured from available abdominal contrast-enhanced computed tomography (CT) scans. Patients were divided into two groups according to the presence of DM. The relationship between PV; biochemical parameters, especially HbA1c; and Mini Nutritional Assessment Short Form (MNAsf) score was analyzed between groups. p < 0.05 was considered statistically significant. Results: The mean age of all participants was M: 77.40, with SD: 7.32. A total of 54.1% of the participants were female, and 55 had DM. There were no significant differences in age and gender between those with and without DM. Glucose (p < 0.001), HbA1C (p < 0.001), and triglycerides (p < 0.001) were significantly higher, and HDL (p < 0.001) was significantly lower in patients with DM. PV was also significantly lower in those with DM (p = 0.028). A correlation analysis revealed significant positive correlations between PV, the MNAsf score (rho (109)) = 0.413, p = 0.003), and lipase (rho (109)) = 0.297, p = 0.002). Conclusions: PV, which is expected to decrease with age, was found to be lower in patients with DM in our study in which we evaluated elderly patients with and without DM. We also found that PV was associated with malnutrition. Our study highlights the importance of determining the clinical effects of pancreatic volume in the geriatric population where organ atrophy is expected. Therefore, we believe that more comprehensive studies are needed to clarify the clinical implications of pancreatic volume on our diagnostic and therapeutic decisions. Full article

Nectins constitute a family of Ca(2+)-independent immunoglobulin-like adhesion molecules. They are involved in cell proliferation, morphogenesis, growth, development, and immune modulation. Due to their broad involvement in physiological processes, extensive research is being conducted on the expression of individual nectins in a variety of cancers and their potential in diagnosis, prognosis, and treatment. The overexpression of nectin-1 may be a poor prognostic factor in gastrointestinal cancers (intestine and pancreas). Similarly, the overexpression of nectin-2 is a worse prognostic factor (greater tumor advancement and shorter patient survival) in cancers such as gallbladder, esophagus, and breast cancer. Changes in nectin-3 expression also affect the advancement of, e.g., colorectal cancer. Additionally, a significant factor here seems to be the change in the localization of nectin-3 expression within cellular structures. The most extensively studied nectin-4 also shows prognostic potential in many cancers. Most often, its high expression correlates with poor prognosis (e.g., gastric cancer), but it may also be a positive prognostic factor, e.g., in salivary gland cancer. Therapy based on nectin-4 is already known and used in the case of urothelial cancers. The expression of nectin-like protein 5 (necl-5) also shows prognostic and therapeutic potential in pancreatic and lung cancers, as well as in multiple myeloma. Full article

Exosomes can transport regulatory biomolecules and are mediators of cellular signaling among metabolic tissues through endocrine mechanisms. Understanding the pathways and processes underlying exosome-mediated inter-tissue communication is critical for elucidating the molecular pathophysiology of metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disorders. Consequently, these mechanisms represent novel and promising targets for pharmacological regulation. We examined the current knowledge regarding exosome physiology, the mechanisms of interaction with target tissues, and its role in metabolic tissue communication. We also analyzed the secretory profiles of exosomes in metabolic tissues, emphasizing their regulatory roles in adipose tissue, liver, pancreas, skeletal muscle, and the small intestine, while discussing their association with metabolic diseases. In this sense, we propose the exosomal pentad as a novel framework highlighting exosome-mediated inter-organ communication, where exosomes may regulate a metabolic axis involving these tissues. This model aligns with the ominous octet in type 2 diabetes but emphasizes exosomes as key regulators of metabolic homeostasis and potential therapeutic targets. The role of exosomes for the treatment of metabolic diseases emerges as a critical area of pharmacologic exploration. For instance, therapeutic strategies that prevent target tissue binding or expression of cargo molecules such as miRNAs could be designed, using antagomiRs or nanoparticles. Additionally, integrins like αvβ5 on the exosomal membrane can be blocked with monoclonal antibodies or engineered for targeted delivery of therapeutic molecules. Exosomes, critical mediators of inter-organ communication and metabolic regulation, hold potential to design precise molecular-level therapies while minimizing systemic side effects. Full article

Gastrointestinal (GI) cancers, which mainly include malignancies of the esophagus, stomach, intestine, pancreas, liver, gallbladder, and bile duct, pose a significant global health burden. Unfortunately, the prognosis for most GI cancers remains poor, particularly in advanced stages. Current treatment options, including targeted and immunotherapies, are less effective compared to those for other cancer types, highlighting an urgent need for novel molecular targets. NEK (NIMA related kinase) kinases are a group of serine/threonine kinases (NEK1-NEK11) that play a role in regulating cell cycle, mitosis, and various physiological processes. Recent studies suggest that several NEK members are overexpressed in human cancers, including gastrointestinal (GI) cancers, which can contribute to tumor progression and drug resistance. Among these, NEK2 stands out for its consistent overexpression in all types of GI cancer. Targeting NEK2 with specific inhibitors has shown promising results in preclinical studies, particularly for gastric and pancreatic cancers. The development and clinical evaluation of NEK2 inhibitors in human cancers have emerged as a promising therapeutic strategy. Specifically, an NEK2 inhibitor, T-1101 tosylate, is currently undergoing clinical trials. This review will focus on the gene expression and functional roles of NEKs in GI cancers, as well as the progress in developing NEK inhibitors. Full article

Anatomy is critical for understanding the physiological and biological adaptations of living creatures. In the case of Pseudopus apodus, an anguimorph lizard belonging to the Order Squamata, it is particularly important considering the scarce previous works on the morphology of its coelomic cavity. It is interesting to consider that, over the years, using non-invasive approaches in reptiles, such as diagnostic imaging methods, is becoming popular for both scientific and clinical purposes. For the present work, we used a total of five Pseudopus apodus individuals (two males and three females); one male and one female were whole-body examined by multi-detector computed tomography (CT) and then all were dissected following a conventional anatomical protocol. The novelty and the main contribution of our multi-detector CT study is to identify structures that had never been identified before using this technique, such as the opening of the vomeronasal organ and the choanae, the tongue, the glottis, the hyoid bone, the esophagus, the stomach, the small and large intestines, the cloaca, the liver, the gallbladder, the kidneys, the ovarian follicles, the trachea, the bronchial bifurcation, the lungs, the heart, the aortic arches, the aorta, the sinus venosus, and the cranial cava veins. On the contrary, other organs like the thyroid, the pancreas, the spleen, the ureters, the urinary bladder, the oviducts, the testes, the hemipenes, the pulmonary trunk, and the pulmonary arteries were only identified in the anatomical dissection. Thus, our results demonstrate that multi-detector CT scanning is a useful tool to identify a significant number of anatomical structures in Pseudopus apodus, which is important for clinical veterinary practice related to this species or different conservation programs, among other applications. Full article

Gonadotropin-inhibitory hormone (GnIH) is well-established as a negative regulator of reproductive physiology and behavior across vertebrates, acting on the hypothalamic–pituitary–gonadal (HPG) axis; however, recent data have also demonstrated its involvement in the control of metabolic processes. GnIH neurons and fibers have been identified in hypothalamic regions associated with feeding behavior and energy homeostasis, with GnIH receptors being expressed throughout the hypothalamus. GnIH does not act alone in the hypothalamus, but rather interacts with the melanocortin system, as well as with other neuropeptides. GnIH and its receptors are also expressed in peripheral tissues involved in important metabolic functions. Therefore, the local action of GnIH in peripheral organs, including the pancreas, gastrointestinal tract, gonad, and adipose tissue, is also suggested. This review aims to provide a comprehensive summary of the emerging role of GnIH in metabolic regulation at both the central and peripheral levels. Full article

The impact of creatine supplementation on individuals with kidney disease or pathological conditions with an increased risk of developing kidney dysfunction remains an active discussion. However, the literature on gene expression related to cellular creatine uptake and metabolism under altered renal function is scarce. Therefore, the present study utilized comprehensive bioinformatics analysis to evaluate the expression of creatine-related genes and to establish their relationships to normal and disturbed renal conditions. We identified 44 genes modulated explicitly in response to creatine exposure from a gene enrichment analysis, including IGF1, SLC2A4, and various creatine kinase genes. The analysis revealed associations with metabolic processes such as amino acid metabolism, indicating a connection between creatine and tissue physiology. Using the Genotype-Tissue Expression Portal, we evaluated their basal tissue-specific expression patterns in kidney and pancreas tissues. Then, we selected several pieces of Gene Expression Omnibus (GEO) transcriptomic data, estimated their expression values, and established relationships to the creatine metabolism pathways and regulation, shedding light on the potential regulatory roles of creatine in cellular processes during kidney diseases. These observations also highlight the connection between creatine and tissue physiology, emphasizing the importance of understanding the balance between endogenous creatine synthesis and creatine uptake, particularly the roles of genes such as GATM, GAMT, SLC6A8, and IGF1, under several kidney dysfunction conditions. Overall, the available data in the biological databases can provide new insights and directions into creatine’s effects and role in renal function. Full article