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https://www.readbyqxmd.com/read/29161325/the-mechanisms-of-humic-substances-self-assembly-with-biological-molecules-the-case-study-of-the-prion-protein
#1
Gabriele Giachin, Ridvan Nepravishta, Walter Mandaliti, Sonia Melino, Alja Margon, Denis Scaini, Pierluigi Mazzei, Alessandro Piccolo, Giuseppe Legname, Maurizio Paci, Liviana Leita
Humic substances (HS) are the largest constituent of soil organic matter and are considered as a key component of the terrestrial ecosystem. HS may facilitate the transport of organic and inorganic molecules, as well as the sorption interactions with environmentally relevant proteins such as prions. Prions enter the environment through shedding from live hosts, facilitating a sustained incidence of animal prion diseases such as Chronic Wasting Disease and scrapie in cervid and ovine populations, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/29157304/a-novel-vector-for-transgenesis-in-the-rat-cns
#2
T Peter Lopez, Kurt Giles, Brittany N Dugger, Abby Oehler, Carlo Condello, Zuzana Krejciova, Julian A Castaneda, George A Carlson, Stanley B Prusiner
The larger brain of the rat enables a much greater repertoire of complex behaviors than mice, likely making rats preferential for investigating neurodegeneration. Because molecular tools for specific expression of transgenes in the rat brain are sparse, we chose Prnp encoding the prion protein (PrP) to develop a novel vector to drive transgene expression in the rat brain. We compared the rat Prnp sequence with mouse and Syrian hamster Prnp sequences, identifying conserved genetic elements and hypothesizing that these elements would be able to drive neuronal transgene expression...
November 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29151170/the-function-of-the-cellular-prion-protein-in-health-and-disease
#3
REVIEW
Joel C Watts, Matthew E C Bourkas, Hamza Arshad
The essential role of the cellular prion protein (PrP(C)) in prion disorders such as Creutzfeldt-Jakob disease is well documented. Moreover, evidence is accumulating that PrP(C) may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer's disease. Although the pathological roles of PrP(C) have been thoroughly characterized, a general consensus on its physiological function within the brain has not yet been established. Knockout studies in various organisms, ranging from zebrafish to mice, have implicated PrP(C) in a diverse range of nervous system-related activities that include a key role in the maintenance of peripheral nerve myelination as well as a general ability to protect against neurotoxic stimuli...
November 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29149024/the-role-of-the-mammalian-prion-protein-in-the-control-of-sleep
#4
REVIEW
Amber Roguski, Andrew C Gill
Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the "eponymous" fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrP(C)), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease...
November 17, 2017: Pathogens
https://www.readbyqxmd.com/read/29138803/toll-like-receptors-tlr1-2-tlr6-and-muc5b-as-binding-interaction-partners-with-cytostatic-proline-rich-polypeptide-1-in-human-chondrosarcoma
#5
Karina Galoian, Silva Abrahamyan, Gor Chailyan, Amir Qureshi, Parthik Patel, Gil Metser, Alexandra Moran, Inesa Sahakyan, Narine Tumasyan, Albert Lee, Tigran Davtyan, Samvel Chailyan, Armen Galoyan
Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma...
November 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29134118/an-overview-of-platelet-products-prp-prgf-prf-etc-in-the-iranian-studies
#6
REVIEW
Seyed Ahmad Raeissadat, Marzieh Babaee, Seyed Mansour Rayegani, Zahra Hashemi, Amir Ali Hamidieh, Parviz Mojgani, Hossein Fouladi Vanda
Aim: The aim of the study was to carry out a review of published studies on various platelet products in Iranian studies. Materials & methods: Electronic databases were searched for relevant articles. Two review authors independently extracted data via a tested extraction sheet, and disagreements were resolved by a meeting with a third review author. Results: Bone disorders (25%), wound and fistula (16%), dental and gingival disorders (14%) and osteoarthritis (11%) have more relative frequency based on different fields...
November 2017: Future Science OA
https://www.readbyqxmd.com/read/29133563/a-promising-anti-prion-trimethoxychalcone-binds-to-the-globular-domain-of-prp-c-and-changes-its-cellular-location
#7
N C Ferreira, L M Ascari, A G Hughson, G R Cavalheiro, C F Góes, P N Fernandes, J R Hollister, R A da Conceição, D S Silva, A M T Souza, M L C Barbosa, F A Lara, R A P Martins, B Caughey, Y Cordeiro
The search for anti-prion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein conversion into protease-resistant forms (PrP(Res) or PrP(Sc)) is a critical step in the development of TSEs, thus being one of the main targets in the screening for anti-prion compounds. In this work, three trimethoxychalcones (J1, J8, J20) and one oxadiazole (Y17), previously identified in vitro as potential anti-prion compounds, were evaluated through different approaches in order to gain inferences about their mechanism of action...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29125811/does-leukocyte-poor-or-leukocyte-rich-platelet-rich-plasma-applied-with-biopolymers-have-superiority-to-conventional-platelet-rich-plasma-applications-on-chondrocyte-proliferation
#8
Duygu Yaşar Şirin, İbrahim Yılmaz, Mehmet İsyar, Kadir Öznam, Mahir Mahiroğulları
OBJECTIVES: This study aims to investigate the possible effects of leukocyte concentration in the content of platelet-rich plasma (PRP) and the administration of PRP using a drug delivery system on chondrocyte proliferation in vitro conditions. PATIENTS AND METHODS: Blood from nine male patients (mean age 65 years; range 49 to 81 years) with advanced stage osteoarthritis who had not responded to medical or conservative treatments and underwent total knee arthroplasty was used to prepare two formulations: PRP with low concentration leukocytes (2000-4000 leukocytes/µL) was designated as pure PRP (P-PRP), whereas PRP with high concentration leukocytes (9000-11000 leukocytes/µL) as leukocyte-rich PRP (L-PRP)...
December 2017: Eklem Hastalıkları Ve Cerrahisi, Joint Diseases & related Surgery
https://www.readbyqxmd.com/read/29102974/inflammatory-optic-disc-neovascularisation-managed-with-oral-steroids-immunosuppressants-and-intravitreal-ranibizumab
#9
Babu Lal Kumawat, Rohan Chawla, Pradeep Venkatesh, Koushik Tripathy
Inflammatory optic disc neovascularisation (NVD) has been treated with periocular or systemic steroids, immunosuppressants, panretinal photocoagulation and bevacizumab. However, the role of intravitreal ranibizumab in inflammatory NVD has not been explored in the peer-reviewed indexed literature. In case 1, NVD and associated subhyaloid haemorrhage showed rapid and dramatic regression after intravitreal ranibizumab. Recurrence was noted 8 weeks after injection which was managed by oral steroids. In case 2, intravitreal ranibizumab led to partial resolution of NVD...
November 3, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29094186/cofactors-influence-the-biological-properties-of-infectious-recombinant-prions
#10
Natalia Fernández-Borges, Michele A Di Bari, Hasier Eraña, Manuel Sánchez-Martín, Laura Pirisinu, Beatriz Parra, Saioa R Elezgarai, Ilaria Vanni, Rafael López-Moreno, Gabriele Vaccari, Vanessa Venegas, Jorge M Charco, David Gil, Chafik Harrathi, Claudia D'Agostino, Umberto Agrimi, Tomás Mayoral, Jesús R Requena, Romolo Nonno, Joaquín Castilla
Prion diseases are caused by a misfolding of the cellular prion protein (PrP) to a pathogenic isoform named PrP(Sc). Prions exist as strains, which are characterized by specific pathological and biochemical properties likely encoded in the three-dimensional structure of PrP(Sc). However, whether cofactors determine these different PrP(Sc) conformations and how this relates to their specific biological properties is largely unknown. To understand how different cofactors modulate prion strain generation and selection, Protein Misfolding Cyclic Amplification was used to create a diversity of infectious recombinant prion strains by propagation in the presence of brain homogenate...
November 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29076011/hepatitis-c-virus-induced-prion-protein-expression-facilitates-hepatitis-c-virus-replication
#11
Huixia Zhang, Shanshan Gao, Rongjuan Pei, Xinwen Chen, Chaoyang Li
Hepatitis C virus (HCV) infects approximately 180 million people worldwide. Significant progress has been made since the establishment of in vitro HCV infection models in cells. However, the replication of HCV is complex and not completely understood. Here, we found that the expression of host prion protein (PrP) was induced in an HCV replication cell model. We then showed that increased PrP expression facilitated HCV genomic replication. Finally, we demonstrated that the KKRPK motif on the N-terminus of PrP bound nucleic acids and facilitated HCV genomic replication...
October 25, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/29074011/analysis-of-reasons-for-noncompliance-with-laser-treatment-in-patients-of-diabetic-retinopathy
#12
Wen Hua, Sijia Cao, Jing Cui, David Maberley, Joanne Matsubara
OBJECTIVE: To identify the underlying reasons for noncompliance among Chinese patients undergoing laser photocoagulation treatment for diabetic retinopathy (DR). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 262 patients with DR with indications for panretinal photocoagulation and focal laser treatment were recruited. METHODS: Those who did not complete the prescribed laser treatment were categorized into 2 types of defaulters: Type 1 defaulters were those who did not initiate laser treatment as scheduled; type 2 defaulters were those who did not complete the entire laser sessions, including terminating midterm or defaulting prompt supplement of laser treatment...
November 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/29058651/estimating-chronic-wasting-disease-susceptibility-in-cervids-using-real-time-quaking-induced-conversion
#13
Nicholas J Haley, Rachel Rielinger, Kristen A Davenport, Katherine O'Rourke, Gordon Mitchell, Jürgen A Richt
In mammals, susceptibility to prion infection is primarily modulated by the host's cellular prion protein (PrP(C)) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both in vivo and in vitro based on PrP(C) amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrP(C) allele conferring absolute resistance in cervids has been identified...
November 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29052140/prion-protein-family-contributes-to-tumorigenesis-via-multiple-pathways
#14
Xiaowen Yang, Zhijun Cheng, Lihua Zhang, Guiru Wu, Run Shi, Zhenxing Gao, Chaoyang Li
A wealth of evidence suggests that proteins from prion protein (PrP) family contribute to tumorigenesis in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC, breast cancer, and gastric cancer. However, the underlying mechanisms remain unclear. The major reasons for cancer cell-caused patient death are metastasis and multiple drug resistance, both of which connect to physiological functions of PrP expressing in cancer cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046463/flow-cytometric-detection-of-prp-sc-in-neurons-and-glial-cells-from-prion-infected-mouse-brains
#15
Takeshi Yamasaki, Akio Suzuki, Rie Hasebe, Motohiro Horiuchi
In prion diseases, an abnormal isoform of prion protein (PrP(Sc)) accumulates in neurons, astrocytes, and microglia in the brains of animals affected with prions. Detailed analyses of PrP(Sc)-positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here we report a novel method for the detection of PrP(Sc) in neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrP(Sc)-specific staining with mAb 132. The combination of PrP(Sc) staining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrP(Sc) from those that were PrP(Sc) negative...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046443/prion-protein-devoid-of-the-octapeptide-repeat-region-delays-bse-pathogenesis-in-mice
#16
Hideyuki Hara, Hironori Miyata, Nandita Rani Das, Junji Chida, Tatenobu Yoshimochi, Keiji Uchiyama, Hitomi Watanabe, Gen Kondoh, Takashi Yokoyama, Suehiro Sakaguchi
Conformational conversion of the cellular isoform of prion protein PrP(C), into the abnormally folded, amyloidogenic isoform, PrP(Sc), is a key pathogenic event in prion diseases including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP(C) into PrP(Sc) after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP-knockout background, designated Tg(PrPΔOR)/Prnp(0/0) mice, did not reduce susceptibility to RML scrapie prions, with abundant accumulation of PrP(Sc)ΔOR in their brains...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29026341/benefits-of-different-postoperative-treatments-in-patients-undergoing-knee-arthroscopic-debridement
#17
Cesáreo Trueba Vasavilbaso, Carlos David Rosas Bello, Erla Medina López, Maria Pilar Coronel Granado, José Mario Navarrete Álvarez, Cesáreo Angel Trueba Davalillo, Félix Isaac Gil Orbezo
PURPOSE: To assess the effectiveness of viscosupplementation or platelet-rich plasma (PRP), compared to standard care, for pain relief after knee arthroscopic debridement in patients with meniscal pathology and osteoarthritis (OA), under normal clinical practice conditions. PATIENTS AND METHODS: We conducted a prospective, randomized, evaluator-blind, pilot study. After arthroscopy, patients were randomized to receive 1) five injections of HA1 (Suprahyal(®)/Adant(®)); 2) four injections of HA2 (Orthovisc(®)); 3) three injections of HA3 (Synvisc(®)); 4) a single injection of PRP (GPS™ II); or 5) standard care (control)...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28989689/semisynthetic-prion-protein-prp-variants-carrying-glycan-mimics-at-position-181-and-197-do-not-form-fibrils
#18
Can Araman, Robert E Thompson, Siyao Wang, Stefanie Hackl, Richard J Payne, Christian F W Becker
The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP(Sc)) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP(C)) into PrP(Sc) and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28978705/an-in-vitro-approach-to-identify-the-key-amino-acids-in-the-low-susceptibility-of-rabbit-prp-to-misfolding
#19
Hasier Eraña, Natalia Fernández-Borges, Saioa R Elezgarai, Chafik Harrathi, Jorge M Charco, Francesca Chianini, Mark P Dagleish, Gabriel Ortega, Óscar Millet, Joaquín Castilla
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of rare progressive neurodegenerative disorders caused by an abnormally folded prion protein (PrP(Sc)). This is capable of transforming the normal cellular prion protein (PrP(C)) in to new infectious PrP(Sc) Interspecies prion transmissibility studies performed by experimental challenge and the outbreak of bovine spongiform encephalopathy that occurred in the late 1980s-1990's showed that while some species were readily susceptible to TSEs (sheep, mice and cats), others were apparently resistant (rabbits, dogs and horses) when exposed to the same agent...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28951092/the-compound-3-5-2-5-dimethoxyphenyl-amino-1-3-4-thiadiazolidin-2-yl-5-8-methoxy-2h-chromen-2-one-inhibits-the-prion-protein-conversion-from-prp-c-to-prp-sc-with-lower-ic50-in-scn2a-cells
#20
Nataraj S Pagadala, Trent C Bjorndahl, Michael Joyce, David S Wishart, Khajamohiddin Syed, Abdolamir Landi
Prion diseases are fatal neurodegenerative disorders of the central nervous system characterized by the accumulation of a protease resistant form (PrP(Sc)) of the cellular prion protein (PrP(C)) in the brain. Two types of cellular prion (PrP(C)) compounds have been identified that appear to affect prion conversion are known as Effective Binders (EBs) and Accelerators (ACCs). Effective binders shift the balance in favour of PrP(C), whereas Accelerators favour the formation of PrP(Sc). Molecular docking indicates EBs and ACCs both bind to pocket-D of the SHaPrP(C) molecule...
September 19, 2017: Bioorganic & Medicinal Chemistry
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