Phaidra - University of Veterinary Medicine Vienna
Not a member yet
3528 research outputs found
Sort by
Malnutrition and Allergies: Tipping the Immune Balance towards Health
No full textMalnutrition, which includes macro- and micronutrient deficiencies, is common in individuals with allergic dermatitis, food allergies, rhinitis, and asthma. Prolonged deficiencies of proteins, minerals, and vitamins promote Th2 inflammation, setting the stage for allergic sensitization. Consequently, malnutrition, which includes micronutrient deficiencies, fosters the development of allergies, while an adequate supply of micronutrients promotes immune cells with regulatory and tolerogenic phenotypes. As protein and micronutrient deficiencies mimic an infection, the body\u27s innate response limits access to these nutrients by reducing their dietary absorption. This review highlights our current understanding of the physiological functions of allergenic proteins, iron, and vitamin A, particularly regarding their reduced bioavailability under inflamed conditions, necessitating different dietary approaches to improve their absorption. Additionally, the role of most allergens as nutrient binders and their involvement in nutritional immunity will be briefly summarized. Their ability to bind nutrients and their close association with immune cells can trigger exaggerated immune responses and allergies in individuals with deficiencies. However, in nutrient-rich conditions, these allergens can also provide nutrients to immune cells and promote health
Targeting Androgen, Thyroid Hormone, and Vitamin A and D Receptors to Treat Prostate Cancer
No full textThe nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR), upon ligand binding and homodimerization, shuttles from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXRs) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and androgen deprivation alone or with chemotherapy is the standard therapy for PCa. RARγ activation and 3,5,3\u27-triiodo-L-thyronine (T3) stimulation of TRβ support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments
Augmentative effects of leukemia inhibitory factor reveal a critical role for TYK2 signaling in vascular calcification
No full textMedial vascular calcification in chronic kidney disease (CKD) involves pro-inflammatory pathways induced by hyperphosphatemia. Several interleukin 6 family members have been associated with pro-calcific effects in vascular smooth muscle cells (VSMCs) and are considered as therapeutic targets. Therefore, we investigated the role of leukemia inhibitory factor (LIF) during VSMC calcification. LIF expression was found to be increased following phosphate exposure of VSMCs. LIF supplementation aggravated, while silencing of endogenous LIF or LIF receptor (LIFR) ameliorated the pro-calcific effects of phosphate in VSMCs. The soluble LIFR mediated antagonistic effects towards LIF and reduced VSMC calcification. Mechanistically, LIF induced phosphorylation of the non-receptor tyrosine-protein kinase 2 (TYK2) and signal transducer and activator of transcription-3 (STAT3) in VSMCs. TYK2 inhibition by deucravacitinib, a selective, allosteric oral immunosuppressant used in psoriasis treatment, not only blunted the effects of LIF, but also interfered with the pro-calcific effects induced by phosphate. Conversely, TYK2 overexpression aggravated VSMC calcification. Ex vivo calcification of mouse aortic rings was ameliorated by Tyk2 pharmacological inhibition and genetic deficiency. Cholecalciferol-induced vascular calcification in mice was improved by Tyk2 inhibition and in the Tyk2-deficient mice. Similarly, calcification was ameliorated in Abcc6/Tyk2-deficient mice after adenine/high phosphorus-induced CKD. Thus, our observations indicate a role for LIF in CKD-associated vascular calcification. Hence, the effects of LIF identify a central pro-calcific role of TYK2 signaling, which may be a future target to reduce the burden of vascular calcification in CKD
Monitoring of Astroviruses, Brno-Hantaviruses, Coronaviruses, Influenza Viruses, Bornaviruses, Morbilliviruses, Lyssaviruses and Pestiviruses in Austrian Bats
No full textHere, we report the results of a monitoring study of bat viruses in Austria to strengthen the knowledge of circulating viruses in Austrian bat populations. In this study, we analyzed 618 oropharyngeal and rectal swab samples from 309 bats and 155 pooled tissue samples from dead bats. Samples were collected from 18 different bat species from multiple locations in Austria, from November 2015 to April 2018, and examined for astroviruses, bornaviruses, coronaviruses, hantaviruses, morbilliviruses, orthomyxoviruses (influenza A/C/D viruses), pestiviruses and rhabdoviruses (lyssaviruses) using molecular techniques and sequencing. Using RT-qPCR, 36 samples revealed positive or suspicious results for astroviruses, Brno-hantaviruses, and coronaviruses in nine different bat species. Further sequencing revealed correspondent sequences in five samples. In contrast, none of the tested samples was positive for influenza viruses A/C/D, bornaviruses, morbilliviruses, lyssaviruses, or pestiviruses
The Mysteries of LETM1 Pleiotropy
No full textLETM1 is a nuclear-encoded protein located in the inner mitochondrial membrane, playing a critical role in regulating mitochondrial cation and volume homeostasis. However, numerous studies on functional features, molecular interactions, and disease-associated effects of LETM1 revealed that LETM1 is also involved in other metabolic functions including glucose utilization, mitochondrial DNA and ribosome organization, cristae architecture and respiratory complex stability. Undisputedly, osmoregulatory processes are essential for mitochondrial functionality, but the pleiotropic aspects of LETM1 challenges us to understand the core function of LETM1, which still remains elusive. In this review, we provide an overview of the current knowledge and latest developments regarding the activities involving LETM1. We highlight various findings that offer different functional perspectives and ideas on the core function of LETM1. Specifically, we emphasize data supporting LETM1\u27s role as a mitochondrial translational factor, K+/H+ exchanger, or Ca2+/H+ exchanger, along with recent findings on its interaction with ATAD3A and TMBIM5. We also present the severe clinical implications of LETM1 deficiency. Finally, we discuss emerging questions raised by the different views on LETM1, which need to be addressed to guide future research directions and ultimately resolve the function of this essential protein and develop targeted therapeutic strategies
The global spread of Oriental Horses in the past 1,500 years through the lens of the Y chromosome
No full textSince their domestication, horses have accompanied mankind, and humans have constantly shaped horses according to their needs through stallion-centered breeding. Consequently, the male-specific portion of the Y chromosome (MSY) is extremely uniform in modern horse breeds. The majority of stallions worldwide carry MSY haplotypes (HT) attributed to an only ~1,500-y-old, so-called, "Crown" haplogroup. The predominance of the Crown in modern horse breeds is thought to represent a footprint of the vast impact of stallions of "Oriental origin" in the past millennium. Here, we report the results of a fine-scaled MSY haplotyping of large datasets of patrilines comprising 1,517 males of 189 modern horse breeds, covering a broad phenotypic and geographic spectrum. We can disentangle the multilayered influence of Oriental stallions over the last few hundred years, exposing the intense linebreeding and the wide-ranging impact of Arabian, English Thoroughbred, and Coldblood sires. Iberian and New World horse breeds contain a wide range of diversified Crown lineages. Their broad HT spectrum illustrates the spread of horses of Oriental origin via the Iberian Peninsula after the Middle Ages, which is commonly referred to as the "Spanish influence." Our survey also revealed a second major historical dissemination of horses from Western Asia, attributed to the expansion of the Ottoman Empire. Our analysis shows that MSY analysis can uncover the complex history of horse breeds and can be used to establish the paternal ancestry of modern horse breeds
Fibrolytic vaccination against ADAM12 reduces desmoplasia in preclinical pancreatic adenocarcinomas
No full textA hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12+ cells reduces fibrosis in various organs. In preclinical mouse models of PDAC, we observe ADAM12 expression in CAFs as well as in tumor cells but not in healthy mouse pancreas. Therefore, we tested prophylactic and therapeutic vaccination against ADAM12 in murine PDAC and observed delayed tumor growth along with a reduction in CAFs and tumor desmoplasia. This is furthermore associated with vascular normalization and alleviated tumor hypoxia. The ADAM12 vaccine induces a redistribution of CD8+ T cells within the tumor and cytotoxic responses against ADAM12+ cells. In summary, vaccination against the endogenous fibroblast target ADAM12 effectively depletes CAFs, reduces desmoplasia and delays the growth of murine PDACs. These results provide proof-of-principle for the development of vaccination-based immunotherapies to treat tumor desmoplasia
Metastasizing dysgerminoma in an inland bearded dragon (Pogona vitticeps)
No full textMalignant dysgerminomas are infrequently reported ovarian neoplasms in animals, especially in exotic pets (non-traditional companion animals [NTCAs]). In the few published case reports on reptilian species, examples are primarily postmortem without antemortem (clinical) assessment.An adult, 13-year-old, spayed female inland bearded dragon (Pogona vitticeps) presented with lethargy, a right-sided head tilt, unilateral exophthalmos and ventrotemporal strabismus on the right eye. On examination, a palpable mass (approximately 3.5 cm in diameter) was detected within the mid coelomic cavity. Computed tomography revealed a retrobulbar swelling and lytic bone lesions affecting the right frontal bone and several vertebrae (T11, T13, and T14). Multiple nodules of soft tissue opacity were also detected within the lungs, liver, and coelomic fat bodies. Haematology revealed leukocytosis with heterophilia and toxic granulation of heterophils. On the basis of these results, differential diagnoses included disseminated abscesses, granulomas (e.g., due to mycobacteriosis) and neoplasms. The lizard was subsequently euthanized due to end-stage disease and a poor prognosis. Postmortem gross examination and histopathology revealed a primary ovarian dysgerminoma with evidence of widespread metastasis as well as localized tissue destruction affecting the right retrobulbar space and frontal bone, the spinal column, the lungs, the liver, and both coelomic fat bodies.This report describes a case of malignant dysgerminoma with widespread intraosseous and visceral metastases in a captive inland bearded dragon (Pogona vitticeps)
Serum Transcobalamin Concentration in Cats-Method Validation and Evaluation in Chronic Enteropathies and Other Conditions
No full textHypocobalaminemia is common in cats with chronic enteropathy (FCE). However, the disruptions in cobalamin metabolism are not fully understood and may vary across species. Cobalamin is distributed to target tissues via binding to transcobalamin (TC) in blood, which has not been evaluated in cats. Thus, an in-house sandwich-ELISA was established to evaluate serum total TC concentrations in cats with FCE. Surplus sera served to analytically validate the assay, and serum TC concentrations were compared among cats with FCE and other diseases (gastrointestinal neoplasia, cholangiohepatopathy, and other neoplastic or non-neoplastic conditions) and healthy controls. Observed-to-expected ratios for serial dilutions ranged from 72.4 to 145.6% and were 75.1-126.7% for spiking-and-recovery. Intra- and inter-assay variability was <17.7% and <17.2% and the preliminary reference interval for feline serum TC was <160-2795 aU/L (lower detection limit: 160 aU/L). Serum TC levels were significantly decreased (p = 0.0067) but not correlated with paired cobalamin concentrations in FCE. Hypertranscobalaminemia predominated with hypercobalaminemia, reaching the highest levels in advanced-stage chronic kidney disease (CKD) cases. TC variations in cobalamin deficiency states with FCE may be linked to inflammation or autoantibodies. This and possible links between serum TC variation in FCE, intracellular cobalamin availability, response to supplementation, and concurrent CKD require further exploratio
Successful treatment of a Himalayan cat with feline orofacial pain syndrome
No full textFeline orofacial pain syndrome is a neuropathic pain disorder in cats, characterised by oral discomfort and tongue self-mutilation. The pathogenesis of feline orofacial pain syndrome remains unclear, but trigger factors such as dental disease and environmental stress have been described. Feline orofacial pain syndrome is a diagnosis of exclusion, and suggested treatment includes administration of non-steroidal anti-inflammatory agents, opioids and adjuvant drugs for analgesia. This case report describes a 4-year-old female Himalayan cat with anorexia, ranula and unilateral lesions of the tongue. Clinical signs ranged from pawing at the mouth to tongue self-mutilation during severe pain attacks. Although no dental disease was present, a dominant and suppressive partner cat may have had a stressful influence. First-line treatment with non-steroidal anti-inflammatory drugs and opioids could not prevent further pain attacks. Successful treatment was achieved with administration of pregabalin and minimisation of potential stress factors. No clinical signs of pain were observed in a follow-up period of 2 years