PARATHYROID HORMONE-RELATED PROTEIN AND PROSTATE CANCER

The survey presents the existing arguments and facts about the parathyroid hormone-related protein (PTHrP) and its role in pathophysiological and pathobio-chemical mechanisms that are related to onco-transformation of prostate. The para-thyroid hormone-related protein is a multipotent molecule, whose proteolytic proc-essing results in the development of smaller biologically active peptides that par-ticipate in the regulation of survival, proliferation and differentiation of cells, in different normal and pathologically changed tissues. The parathyroid hormone-related protein is produced by prostate cancer cells and many other tumors. The au-thors put their special attention to biochemical basis of mechanisms that cause ef-fects related to parathyroid hormone-related protein at patients with prostate can-cer. The survey covers the question of how the parathyroid hormone-related pro-tein participates in modulation of phenotypic developments of the onco-transformation if its tissue, as well as its role in formation of local and whole or-ganism reactions in response to the prostate cancer treatment. The main attention was devoted to the influence of the parathyroid hormone-related protein on the key effects in the development of cancer in natural conditions. The final remarks reflect the existing and potential possibilities to use the modern knowledge about the para-thyroid hormone-related protein in the clinical practice on the prostate cancer for the diagnostic purposes, as well as the targets for the anticancer therapy. The survey presents the data on the structure, biochemical characteristics and multifaceted role of this protein in the organism. The main part of the survey contains information about the different aspects of participation of the parathyroid hormone-related protein in development of the prostate cancer, in its metastasizing, the role in development of hormoneresistance, effect on apoptosis in prostate can-cer cells

The role of calcium metabolism disorders in the formation of different density calculi with calcium oxalate nephrolithiasis

Objective To investigate the relationship between calcium metabolism disorders, stone formation inhibitor levels and stone density in primary and recurrent calcium-oxalate nephrolithiasis.Material and Methods Sixty nine patients with urolithiasis were examined, their average age was 41,4 ± 9,5 years. Two main groups were distinguished: Group 1 – primary calcium-oxalate nephrolithiasis (PN), Group 2 – recurrent calcium-oxalate nephrolithiasis (RN). Then each group was divided into two subgroups – A and B according to stone density: 500–1000 HU and from 1000–1500 HU, respectively. Stone density was determined by computed tomography (CT). PTH (parathormone), PTHrP (parathyroid hormone related protein), vitamin D, total blood calcium (Ca), ionized blood Ca, total blood protein, Ca and urine pH were also examined. After the examination, patients underwent surgical removal of the stones.Results It was found that 41.9% of group 1 and 46.9% of group 2 patients had grade I obesity. Average creatinine level in group 2 was 9.7% higher than in group 1 (p < 0.05). Urea level in both groups was not statistically significantly different. Glomerular filtration rate (GFR) was comparable. Groups 2A and 2B had higher PTHrP values (77.61 and 76.98 pg/mL, respectively) combined with relatively high PTH levels (2A – 4.4 pg/mL and 2B – 5.1 pg/mL), relatively low osteopontin concentration (2A – 0.044 pg/ mL, 2B – 1.106 pg/mL), compared to those in group 1 (p < 0.05). Pairwise unidirectional differences between groups 1A and 2A, 1B and 2B were found to correlate positively with density values: for osteopontin: r = 0.992 (p < 0.05); for vitamin D: r = 0.831 (p < 0.05); for blood Ca2+ ions: r = 0.836 (p < 0.05); for urine pH: r = 0.863 (p < 0.05). There was a negative correlation with the daily concentration of urinary calcium ions with the density of concrements: r = -0.663; p < 0.05. The concentration of osteopontin was significantly higher in Group 1B and 2B patients, and it was significantly lower in patients with stones of < 1000 HU density. Higher values of osteopontin concentration were noted in groups 1B and 2B in relation to groups 1A (p < 0.05) and 2A (p < 0.05). The increase of blood Ca2+ ions in patients in groups 1B and 2B in relation to groups 1A (p < 0.05) and 2A (p < 0.05) was also accompanied by higher values of vitamin D.Conclusion Patients with denser stones showed high values of osteopontin and PTHrP in serum and low values of urinary calcium ions, which may lead to the formation of concrements on the matrix with an organic base. Determination of calcium metabolism makes it possible to predict recurrence of KSD in primary calcium oxalate nephrolithiasis and assess the severity of mineral metabolism disorders in recurrent calcium oxalate nephrolithiasis

Role of parathyroid hormone-related protein in breast cancer detection and prognosis

Currently, there are limited data supporting the use of parathyroid hormone-related protein for the purposes of breast cancer detection and disease prognosis. This literature review covers research results on diagnostic potential of parathyroid hormone-related protein as a biomarker for breast cancer, as well as the information available in the scientific literature, reflecting obvious contradictions regarding clinical and prognostic importance of this protein in the primary breast cancer, correlation of its expression with the risk of bone metastasis and survival of patients. Results of preclinical and clinical research show, that parathyroid hormone-related protein inhibits tumor progression and decreases its metastasis at early stages of the disease, which improves the survival rate, but it has an opposite effect at the advanced stages of cancer, as it increases tumor development and metastasis, and reduces survival rates. Altogether, these studies prove an idea that parathyroid hormone-related protein plays a double role in breast cancer. Use of parathyroid hormone-related protein for breast cancer early detection and disease prognosis is currently becoming a subject of detailed scientific research studies, which is confirmed by the facts presented in this literature review

MODELING OF BONE INJURIES IN ANIMAL EXPERIMENTS

In this review, we discuss the advantages and disadvantages of the existing bone defect animal models and tissue engineering techniques applied in studying novel bone defect regenerative approaches. The paper suggests the requirements for an optimal animal model, as well as analyzes in vivo bone injury models widely used in testing. The authors briefly review the methods of experimentally produced lesions of long bones, calvarial bones, mandibular bones in different animals. This review also describes the standardization techniques allowing one to evaluate the process of osteogenesis and bone-implant interactions. That will help researchers thoroughly plan and conduct experiments according to the bioethical principles

Parathyroid hormone-related protein as predictor of urolithiasis disease development

Background. The present article studies a possible role of parathyroid hormone-related protein (PTHrP) in urolithiasis pathogenesis.Aim. To consider PTHrP level as a predictor of the urolithiasis development.Material and Methods. We presented an analysis of treatment in 79 patients with primary and recurrent nephrolithiasis that had underwent surgical treatment in the Uronephrological Center of Scientific Research Institute – Ochapovsky Regional Clinical Hospital no. 1, Krasnodar from 2017 to 2019. All observed patients were divided in two groups: patients with primary and recurrent nephrolithiasis. A group of 10 relatively healthy people was included in the study as well. All patients and conditionally healthy people had a test for blood parameters; in particular, the level of parathyroid hormone-related protein was assessed in order to compare the indicators in all three groups.Conclusions. The PTHrP level was showed to be statistically significantly different in patients with urolithiasis from the group with relatively healthy people. Groups with primary and recurrent nephrolithiasis show not difference in the level of PTHrP. Further studies are necessary to consider this protein as one of the predictors of urolithiasis and study its role in the pathogenesis of nephrolithiasis

Biochemical aspects of magnesium-enhanced bone regeneration

Current research is focused on practical implications of magnesium-based implants largely due to their biodegradability and ability to promote bone healing and formation. However, the mechanism underlying the osteogenesis regulation by magnesium is still unclear.We describe cellular and molecular mechanisms underlying the effect of magnesium ions (Mg2+) on bone growth following the device implantation. The presented data demonstrate magnesium-induced activation of canonical Wnt/β-catenin signaling pathway in human bone marrow stromal cells resulting in their differentiation into osteoblasts, osteogenic effect and recovery of bone defects. We describe the role of the molecular mechanisms responsible for osteopromotive properties of Mg2+ and associated with unique transient receptor potential melastatin 7 (TRPM7) cation channels mediating the Mg2+ influx. TRPM7-mediated Mg2+ influx is important for platelet-derived growth factor (PDGF)-induced proliferation, adhesion, and migration of human osteoblasts, as well as for promotion of Mg2+-associated bone regeneration.We discuss the effect of Mg2+ on intracellular signaling processes, expression of the vascular endothelial growth factor (VEGF), hypoxia-inducible factor-2α, and peroxisome proliferator-activated receptor-γ coactivator 1α. Mg2+ can promote bone regeneration by enhancing the production of type X collagen and VEGF by osteogenic cells in bone marrow

Neurocranial osteology and neuroanatomy of a late Cretaceous Titanosaurian Sauropod from Spain (Ampelosaurus sp.)

Titanosaurians were a flourishing group of sauropod dinosaurs during Cretaceous times. Fossils of titanosaurians have been found on all continents and their remains are abundant in a number of Late Cretaceous sites. Nonetheless, the cranial anatomy of titanosaurians is still very poorly known. The Spanish latest Cretaceous locality of "Lo Hueco" yielded a relatively well preserved, titanosaurian braincase, which shares a number of phylogenetically restricted characters with Ampelosaurus atacis from France such as a flat occipital region. However, it appears to differ from A. atacis in some traits such as the greater degree of dorsoventral compression and the presence of proatlas facets. The specimen is, therefore, provisionally identified as Ampelosaurus sp. It was CT scanned, and 3D renderings of the cranial endocast and inner-ear system were generated. Our investigation highlights that, although titanosaurs were derived sauropods with a successful evolutionary history, they present a remarkably modest level of paleoneurological organization. Compared with the condition in the basal titanosauriform Giraffatitan brancai, the labyrinth of Ampelosaurus sp. shows a reduced morphology. The latter feature is possibly related to a restricted range of head-turning movementsThis is a contribution to the research project CGL2009-12143 (Ministerio de Economía y Competitividad, Madrid), of which FK, who is currently supported by the Ramón y Cajal Program, is Principal Investigator. LMW and RCR acknowledge funding support from the United States National Science Foundation (IBN-9601174, IBN-0343744, IOB-0517257, IOS-1050154) and the Ohio University Heritage College of Osteopathic Medicine. The Ohio Supercomputing Center also provided suppor

Hip joint articular soft tissues of non-dinosaurian Dinosauromorpha and early Dinosauria: evolutionary and biomechanical implications for Saurischia

Dinosauromorphs evolved a wide diversity of hind limb skeletal morphologies, suggesting highly divergent articular soft tissue anatomies. However, poor preservation of articular soft tissues in fossils has hampered any follow-on functional inferences. We reconstruct the hip joint soft tissue anatomy of non-dinosaurian dinosauromorphs and early dinosaurs using osteological correlates derived from extant sauropsids and infer trends in character transitions along the theropod and sauropodomorph lineagues. Femora and pelves of 107 dinosauromorphs and outgroup taxa were digitized using 3D imaging techniques. Key transitions were estimated using maximum likelihood ancestral state reconstruction. The hips of dinosauromorphs possessed wide a disparity of soft tissue morphologies beyond the types and combinations exhibited by extant archosaurs. Early evolution of the dinosauriform hip joint was characterized by the retention of a prominent femoral hyaline cartilage cone in post-neonatal individuals, with the cartilage cone independently reduced within theropods and sauropodomorphs. The femur of Dinosauriformes possessed a fibrocartilage sleeve on the metaphysis, which surrounded a hyaline core. The acetabulum of Dinosauriformes possessed distinct labrum and antitrochanter structures. In sauropodomorphs, hip congruence was maintained by thick hyaline cartilage on the femoral head, whereas theropods relied on acetabular tissues such as ligaments and articular pads. In particular, the craniolaterally ossified hip capsule of non- Avetheropoda neotheropods permitted mostly parasagittal femoral movements. These data indicate that the dinosauromorph hip underwent mosaic evolution within the saurischian lineage and that sauropodomorphs and theropods underwent both convergence and divergence in articular soft tissues, correlated with transitions in body size, locomotor posture, and joint loading

The Predatory Ecology of Deinonychus and the Origin of Flapping in Birds

Most non-avian theropod dinosaurs are characterized by fearsome serrated teeth and sharp recurved claws. Interpretation of theropod predatory ecology is typically based on functional morphological analysis of these and other physical features. The notorious hypertrophied ‘killing claw’ on pedal digit (D) II of the maniraptoran theropod Deinonychus (Paraves: Dromaeosauridae) is hypothesized to have been a predatory adaptation for slashing or climbing, leading to the suggestion that Deinonychus and other dromaeosaurids were cursorial predators specialized for actively attacking and killing prey several times larger than themselves. However, this hypothesis is problematic as extant animals that possess similarly hypertrophied claws do not use them to slash or climb up prey. Here we offer an alternative interpretation: that the hypertrophied D-II claw of dromaeosaurids was functionally analogous to the enlarged talon also found on D-II of extant Accipitridae (hawks and eagles; one family of the birds commonly known as “raptors”). Here, the talon is used to maintain grip on prey of subequal body size to the predator, while the victim is pinned down by the body weight of the raptor and dismembered by the beak. The foot of Deinonychus exhibits morphology consistent with a grasping function, supportive of the prey immobilisation behavior model. Opposite morphological trends within Deinonychosauria (Dromaeosauridae + Troodontidae) are indicative of ecological separation. Placed in context of avian evolution, the grasping foot of Deinonychus and other terrestrial predatory paravians is hypothesized to have been an exaptation for the grasping foot of arboreal perching birds. Here we also describe “stability flapping”, a novel behaviour executed for positioning and stability during the initial stages of prey immobilisation, which may have been pivotal to the evolution of the flapping stroke. These findings overhaul our perception of predatory dinosaurs and highlight the role of exaptation in the evolution of novel structures and behaviours

A basal lithostrotian titanosaur (Dinosauria: Sauropoda) with a complete skull: Implications for the evolution and paleobiology of titanosauria

We describe Sarmientosaurus musacchioi gen. et sp. nov., a titanosaurian sauropod dinosaur from the Upper Cretaceous (Cenomanian - Turonian) Lower Member of the Bajo Barreal Formation of southern Chubut Province in central Patagonia, Argentina. The holotypic and only known specimen consists of an articulated, virtually complete skull and part of the cranial and middle cervical series. Sarmientosaurus exhibits the following distinctive features that we interpret as autapomorphies: (1) maximum diameter of orbit nearly 40% rostrocaudal length of cranium; (2) complex maxilla - lacrimal articulation, in which the lacrimal clasps the ascending ramus of the maxilla; (3) medial edge of caudal sector of maxillary ascending ramus bordering bony nasal aperture with low but distinct ridge; (4) ´tongue-like´ ventral process of quadratojugal that overlaps quadrate caudally; (5) separate foramina for all three branches of the trigeminal nerve; (6) absence of median venous canal connecting infundibular region to ventral part of brainstem; (7) subvertical premaxillary, procumbent maxillary, and recumbent dentary teeth; (8) cervical vertebrae with ´strut-like´ centroprezygapophyseal laminae; (9) extremely elongate and slender ossified tendon positioned ventrolateral to cervical vertebrae and ribs. The cranial endocast of Sarmientosaurus preserves some of the most complete information obtained to date regarding the brain and sensory systems of sauropods. Phylogenetic analysis recovers the new taxon as a basal member of Lithostrotia, as the most plesiomorphic titanosaurian to be preserved with a complete skull. Sarmientosaurus provides a wealth of new cranial evidence that reaffirms the close relationship of titanosaurs to Brachiosauridae. Moreover, the presence of the relatively derived lithostrotian Tapuiasaurus in Aptian deposits indicates that the new Patagonian genus represents a ´ghost lineage´ with a comparatively plesiomorphic craniodental form, the evolutionary history of which is missing for at least 13 million years of the Cretaceous. The skull anatomy of Sarmientosaurus suggests that multiple titanosaurian species with dissimilar cranial structures coexisted in the early Late Cretaceous of southern South America. Furthermore, the new taxon possesses a number of distinctive morphologies - such as the ossified cervical tendon, extremely pneumatized cervical vertebrae, and a habitually downward- facing snout - that have rarely, if ever, been documented in other titanosaurs, thus broadening our understanding of the anatomical diversity of this remarkable sauropod clade. The latter two features were convergently acquired by at least one penecontemporaneous diplodocoid, and may represent mutual specializations for consuming low-growing vegetation.Fil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia; ArgentinaFil: Lamanna, Matthew C.. Carnegie Museum Of Natural History; Estados UnidosFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "bernardino Rivadavia"; ArgentinaFil: Ridgely, Ryan C.. Ohio University College Of Osteopathic Medicine; Estados UnidosFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Javier E.. Hospital Regional de Comodoro Rivadavia; ArgentinaFil: Vita, Javier R.. Resonancia Magnética Borelli; ArgentinaFil: Witmer, Lawrence M.. Ohio University College Of Osteopathic Medicine; Estados Unido