Search Results (8)

Down syndrome (DS), the most common survivable autosomal aneuploidy, is associated with a high prevalence of congenital anomalies of the kidney and urinary tract (CAKUT), significantly increasing the risk of chronic kidney disease (CKD). This review examines the diversity of CAKUT phenotypes reported in individuals with DS, focusing on anomalies affecting the kidney, ureter, bladder, and urethra. According to available literature, hydronephrosis is the most common renal anomaly, often secondary to other CAKUT phenotypes, followed by renal hypoplasia and glomerulocystic disease. Furthermore, obstructive uropathies are also frequent but usually lack detailed characterization in the literature. Key features of CAKUT in DS, including reduced kidney size, renal cystic diseases, acquired glomerulopathies, reduced nephron number, and immature glomeruli heighten the risk of CKD. Also, early detection of lower urinary tract dysfunction (LUTD) is critical to prevent progressive upper urinary tract damage and CKD. Despite the prevalence of CAKUT in DS, reported between 0.22% and 21.16%, there is a lack of standardized diagnostic criteria, consistent terminology, and extended follow-up studies. Systematic screening from infancy, including regular renal monitoring via urinalysis and ultrasound, plays a critical role in the timely diagnosis and intervention of CAKUT. To further enhance diagnostic accuracy and develop effective therapeutic strategies, increased awareness and focused research into the genetic factors underlying these anomalies are essential. Moreover, a multidisciplinary approach is indispensable for managing CAKUT and its associated complications, ultimately ensuring better long-term outcomes and an improved quality of life for individuals with DS. Full article

Human pluripotent stem cells have been employed in generating organoids, yet their immaturity compared to fetal organs and the limited induction of all constituent cell types remain challenges. Porcine fetal progenitor cells have emerged as promising candidates for co-culturing with human progenitor cells in regeneration and xenotransplantation research. This study focused on identifying proper preservation methods for porcine fetal kidneys, hearts, and livers, aiming to optimize their potential as cell sources. Extracted from fetal microminiature pigs, these organs were dissociated before and after cryopreservation–thawing, with subsequent cell quality evaluations. Kidney cells, dissociated and aggregated after vitrification in a whole-organ form, were successfully differentiated into glomeruli and tubules in vivo. In contrast, freezing hearts and livers before dissociation yielded suboptimal results. Heart cells, frozen after dissociation, exhibited pulsating heart muscle cells similar to non-frozen hearts. As for liver cells, we developed a direct tissue perfusion technique and successfully obtained highly viable liver parenchymal cells. Freezing dissociated liver cells, although inferior to their non-frozen counterparts, maintained the ability for colony formation. The findings of this study provide valuable insights into suitable preservation methods for porcine fetal cells from kidneys, hearts, and livers, contributing to the advancement of regeneration and xenotransplantation research. Full article

Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte–macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy. Full article

This study aims to determine the protein expression patterns of acetylated α-tubulin, inversin, dishevelled-1, Wnt5a/b, and β-catenin in developing (E13.5 and E15.5) and early postnatal (P4 and P14) kidneys of Dab1^−/− (yotari) mice, their role in regulating the Wnt signaling pathway, and the possible relation to congenital anomalies of kidney and urinary tract (CAKUT). The analysis of target protein co-expression, observed in the renal vesicles/immature glomeruli, ampullae/collecting ducts, convoluted tubules, metanephric mesenchyme of developing kidneys, but proximal convoluted tubules, distal convoluted tubules and glomeruli of postnatal kidneys, was performed using double immunofluorescence and semi-quantitative methods. The overall expression of acetylated α-tubulin and inversin during normal kidney development increases with higher expression in yotari mice as the kidney acquires mature morphology. An increase in β-catenin and cytosolic DVL-1 levels, indicating a switch from non-canonical to canonical Wnt signaling, is found in the postnatal kidney of yotari mice. In contrast, healthy mouse kidney expresses inversin and Wnt5a/b in the postnatal period, thus activating non-canonical Wnt signaling. Target protein expression patterns in kidney development and the early postnatal period observed in this study could indicate that switching between canonical and non-canonical Wnt signaling is crucial for normal nephrogenesis, while the defective Dab1 gene product in yotari mice may promote CAKUT due to interfering with this process. Full article

The effect of the homocysteine toxicity on both mother and embryo is known to induce disruption of placental blood flow and disturbances of the brain formation in offspring. The mechanisms of these effects are poorly understood and should be studied. The effects of prenatal hyperhomocysteinemia (pHHC) on the expression of some neuronal genes, neural tissue maturation and neuronal migration were analyzed in this study. Hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution during pregnancy. On P5–P20 some features of developmental delay were observed in both cortical and hippocampus tissue ultrastructure in pHHC pups, accompanied by a retardation in body weight and motor development. In hippocampus tissue of P20 pHHC pups of synaptic glomeruli were absence suggesting more essential tissue immaturity compared to the cortical one. In pHHC pupst was shown decreased number and disturbed positioning of the neuronal cells labeled on E14 or E18, suggesting decrease in generation of cortical neuroblasts and disturbance in their radial migration into the cortical plate. On E14 the expression of the Kdr gene (an angiogenesis system component) was decreased in pHHC fetus brains. The content of SEMA3E and the MMP-2 activity level was increased. On E20 the increase in proBDNF/mBDNF ratio was also shown in pHHC pups, it might affect positioning maturation and viability of neuronal cell. The activation of caspase-3 accompanied by decrease in the level of procaspase-8 in the brain tissue of E20 pHHC fetuses may suggest the presence of cell apoptosis. It can be concluded that pHHC disturbs the mechanisms of early brain development and delay in brain tissue maturation in both neocortex and hippocampus of pups during early postnatal ontogenesis. Full article

Urine testing is a convenient, non-invasive method of obtaining information about body functions. Depending on the intended purpose, urine testing may be qualitative and/or quantitative. Urine analysis can also include proteins. There are no data in the literature on the occurrence of proteinuria in healthy neonatal calves. The present study was the first that aimed to quantify the hypothesis of proteinuria occurrence in these animals in the first week of life, to assess its intensity and dynamics and to understand the underlying causes of proteinuria in healthy calves. The research was carried out on 15 healthy calves in the first seven days of life. Calves were catheterized to determine minute diuresis. Total protein concentration was determined in blood plasma and urine. Urine proteins were separated by electrophoresis (SDSPAGE) and their concentration and percentage were determined by densitometry using an image archiving and analysis software. The separated proteins were divided into three groups according to molecular weight for albumin, LMW and HMW proteins. The results were standardized per 1 m² of body surface area and statistically analyzed. Neonatal proteinuria was demonstrated in healthy calves, mainly resulting from the high concentration of LMW proteins in the urine. Their percentages decreased significantly from 84.46% on the first day of calves’ life to 64.02% on day 7. At the same time, a statistically significant increase was observed in the proportion of albumin and high molecular weight proteins in urine total protein. Albumin percentage increased from 9.54% (on day 1) to almost 20% (on day 7), while the proportion of HMW proteins increased from 6.68% to 18.13%, respectively. The concentration of total protein in the urine of newborn calves amounted to 14.64 g/L and decreased statistically significantly during the first 72 h of postnatal life, stabilizing at the level of 3–4 g/L. The mean value of total protein excretion in the first week of life was 4.81 mg/min/m² (i.e., 6.93 g/24 h/m²). The analysis of protein concentration in the urine and its excretion, as well as changes in urinary excretion of the tested protein fractions, indicated that neonatal proteinuria in healthy neonatal calves was tubular (i.e., main reason is the reduced absorption of proteins in nephrons). In addition, research showed that there was a rapid improvement in resorptive mechanisms in tubular cells. It should be assumed that the filtration barrier in the kidneys of these animals after birth is morphologically prepared to retain high molecular weight proteins. It seems that the increased permeability of the filtration barrier in the glomeruli does not necessarily indicate the immaturity of the kidneys, but may indicate the kidneys’ adaptation to excess protein removal from the body during feeding with high-protein food (colostrum), with an open intestinal barrier enabling protein absorption from the gastrointestinal tract to the blood. Full article

Renal maldevelopment (RM) has been proposed to replace the old and sometimes misused term “renal dysplasia” in dogs. Although renal dysplasia has been described in Boxers, hereditary transmission has only been hypothesized. This study reports clinical and renal histological findings in Boxer dogs with RM, proposing a possible mode of inheritance. Medical records of 9 female Boxer dogs, older than 5 months and with a clinical diagnosis of chronic kidney disease prior to one year of age, were retrospectively reviewed. Polyuria and polydipsia (PU/PD), decreased appetite, weight loss, lethargy and weakness were described in all affected dogs. Common laboratory findings were proteinuria, diluted urine, non-regenerative anemia, azotemia, hyperphosphatemia, hypoalbuminemia and hypercholesterolemia. Histopathology of the kidneys revealed the presence of immature glomeruli in all dogs, which is consistent with RM. In 7 related dogs, the pedigree analysis showed that a simple autosomal recessive trait may be a possible mode of inheritance. Renal maldevelopment should be suspected in young Boxer dogs with a history of PU/PD, decreased appetite, weight loss, lethargy, weakness and proteinuria. Due to its possible inheritance, an early diagnosis of RM may allow clinicians to promptly identify other potentially affected dogs among the relatives of the diagnosed case. Full article

The carotid body (CB), a neural-crest-derived organ and the main arterial chemoreceptor in mammals, is composed of clusters of cells called glomeruli. Each glomerulus contains neuron-like, O₂-sensing glomus cells, which are innervated by sensory fibers of the petrosal ganglion and are located in close contact with a dense network of fenestrated capillaries. In response to hypoxia, glomus cells release transmitters to activate afferent fibers impinging on the respiratory and autonomic centers to induce hyperventilation and sympathetic activation. Glomus cells are embraced by interdigitating processes of sustentacular, glia-like, type II cells. The CB has an extraordinary structural plasticity, unusual for a neural tissue, as it can grow several folds its size in subjects exposed to sustained hypoxia (as for example in high altitude dwellers or in patients with cardiopulmonary diseases). CB growth in hypoxia is mainly due to the generation of new glomeruli and blood vessels. In recent years it has been shown that the adult CB contains a collection of quiescent multipotent stem cells, as well as immature progenitors committed to the neurogenic or the angiogenic lineages. Herein, we review the main properties of the different cell types in the CB germinal niche. We also summarize experimental data suggesting that O₂-sensitive glomus cells are the master regulators of CB plasticity. Upon exposure to hypoxia, neurotransmitters and neuromodulators released by glomus cells act as paracrine signals that induce proliferation and differentiation of multipotent stem cells and progenitors, thus causing CB hypertrophy and an increased sensory output. Pharmacological modulation of glomus cell activity might constitute a useful clinical tool to fight pathologies associated with exaggerated sympathetic outflow due to CB overactivation. Full article