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https://www.readbyqxmd.com/read/29050400/metformin-reverses-trap1-mutation-associated-alterations-in-mitochondrial-function-in-parkinson-s-disease
#1
Julia C Fitzgerald, Alexander Zimprich, Daniel A Carvajal Berrio, Kevin M Schindler, Brigitte Maurer, Claudia Schulte, Christine Bus, Anne-Kathrin Hauser, Manuela Kübler, Rahel Lewin, Dheeraj Reddy Bobbili, Lisa M Schwarz, Evangelia Vartholomaiou, Kathrin Brockmann, Richard Wüst, Johannes Madlung, Alfred Nordheim, Olaf Riess, L Miguel Martins, Enrico Glaab, Patrick May, Katja Schenke-Layland, Didier Picard, Manu Sharma, Thomas Gasser, Rejko Krüger
The mitochondrial proteins TRAP1 and HTRA2 have previously been shown to be phosphorylated in the presence of the Parkinson's disease kinase PINK1 but the downstream signalling is unknown. HTRA2 and PINK1 loss of function causes parkinsonism in humans and animals. Here, we identified TRAP1 as an interactor of HTRA2 using an unbiased mass spectrometry approach. In our human cell models, TRAP1 overexpression is protective, rescuing HTRA2 and PINK1-associated mitochondrial dysfunction and suggesting that TRAP1 acts downstream of HTRA2 and PINK1...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29049632/an-engineering-model-to-test-for-sensory-reweighting-in-non-human-primate-posture
#2
Lara A Thompson, Csilla Haburcakova, Adam D Goodworth, Richard F Lewis
Quantitative animal models are critically needed to provide proof-of-concept for the investigation of rehabilitative balance therapies (e.g., invasive vestibular prostheses) and treatment response prior to, or in conjunction with, human clinical trials. This paper describes a novel approach to modeling the non-human primate postural control system. Our observation that rhesus macaques and humans have even remotely similar postural control motivates the further application of the rhesus macaque as a model for studying the effects of vestibular dysfunction, as well as vestibular prosthesis-assisted states, on human postural control...
October 10, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/29049003/-tau-immunotherapy-hopes-and-hindrances
#3
Koorosh Shahpasand, Alireza Sepehri Shamloo, Seyed Massood Nabavi, Xiao Zhen Zhou, Kun Ping Lu
Alzheimer's disease (AD) is a progressive neurological disorder having two major pathological hallmarks: the extracellular senile plaques and intracellular neurofibrillary tangles composed of amyloid beta protein and hyperphosphorylated tau respectively. Removal of protein deposits from AD brains are the newer attempts for treating AD. The major developments in this direction have been the amyloid and tau based therapeutics. While senile plaque removal employing monoclonal antibodies (mAbs) restore brain function in mouse models of AD, tau has been recently introduced as the major neurodegenerative factor mediating neural cell death...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29048662/capsaicin-inhibits-proliferation-and-induces-apoptosis-in-osteosarcoma-cell-lines-via-the-mitogen%C3%A2-activated-protein-kinase-pathway
#4
Yuan Zhang, Xu Deng, Tao Lei, Chang Yu, Yang Wang, Guosheng Zhao, Xiaoji Luo, Ke Tang, Zhengxue Quan, Dianming Jiang
Capsaicin, a pungent molecular compound present in many hot peppers, exerts anticancer activities against various human cancer cell lines by inducing apoptosis. However, the effects of capsaicin on human osteosarcoma (OS) as well as the related mechanisms remain to be fully elucidated. In the present study, the anticancer effects of capsaicin on 3 human OS cell lines (MG63, 143B and HOS) were investigated. Various concentrations of capsaicin (50-300 µM) effectively decreased cell viability in all 3 OS cell lines in a dose-dependent manner...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29047086/natural-antioxidants-as-potential-therapy-and-a-promising-role-for-melatonin-against-pulmonary-hypertension
#5
Gerald J Maarman
Plasma and serum samples, and lung/heart tissue of pulmonary hypertension (PH) patients and animal models of PH display elevated oxidative stress. Moreover, the severity of PH and levels of oxidative stress increase concurrently, which suggests that oxidative stress could be utilized as a biomarker for PH progression. Accumulating evidence has well established that oxidative stress is also key role player in the development of PH. Preclinical studies have demonstrated that natural antioxidants improved PH condition, and, therefore, antioxidant therapy has been proposed as a potential therapeutic strategy against PH...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046353/a-mechanistic-model-to-predict-effects-of-cathepsin-b-and-cystatin-c-on-%C3%AE-amyloid-aggregation-and-degradation
#6
Tyler J Perlenfein, Regina M Murphy
β-Amyloid (Aβ) aggregation is thought to initiate a cascade of neurodegenerative events in Alzheimer's disease (AD). Much effort is underway to develop strategies to reduce Aβ concentration or inhibit aggregation. Cathepsin B (CatB) proteolytically degrades Aβ into nonaggregating fragments, but is potently inhibited by cystatin C (CysC). It has been suggested that decreasing CysC would facilitate Aβ clearance by relieving CatB inhibition. On the other hand, CysC binds Aβ and inhibits Aβ aggregation, suggesting that an intervention that increases CysC would prevent Aβ aggregation...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29046310/protein-structure-facilitates-high-resolution-immunological-mapping
#7
Madison Zuverink, Joseph T Barbieri
Select Agents (SA) pose unique challenges towards licensing vaccines and therapies. In the case of toxin-mediated diseases, Health and Human Services assign guidelines for SA use, oversee vaccine and therapy development, and approve animal models and approaches to identify mechanism(s) for toxin neutralization. In this commentary, we discuss next generation vaccines and therapies against ricin toxin and botulinum toxin, SA-regulated toxins, which utilize structure-based approaches for counter measures to guide rapid response to future biothreats...
October 18, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/29046072/commentary-on-the-clinical-and-preclinical-dosage-limits-of-interstitially-administered-magnetic-fluids-for-therapeutic-hyperthermia-based-on-current-practice-and-efficacy-models
#8
Paul Southern, Quentin A Pankhurst
We offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field...
October 18, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29046006/-skin-and-soft-tissue-infections-due-to-corynebacterium-ulcerans-case-reports
#9
Christian Jenssen, Ilona Schwede, Volker Neumann, Cristine Pietsch, Werner Handrick
History and clinical findings We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases...
October 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29045731/the-chimpanzee-model-of-viral-hepatitis-advances-in-understanding-the-immune-response-and-treatment-of-viral-hepatitis
#10
Robert E Lanford, Christopher M Walker, Stanley M Lemon
Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations...
October 17, 2017: ILAR Journal
https://www.readbyqxmd.com/read/29045045/mesenchymal-stromal-cell-therapy-in-bronchopulmonary-dysplasia-systematic-review-and-meta-analysis-of-preclinical-studies
#11
Sajit Augustine, Marc T Avey, Brittany Harrison, Tiffany Locke, Mona Ghannad, David Moher, Bernard Thébaud
Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM)...
October 17, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29044980/phenotypic-and-genotypic-profile-of-clinical-and-animal-multi-drug-resistant-salmonella-enterica-isolates-from-mexico
#12
S Aguilar-Montes de Oca, M Talavera-Rojas, E Soriano-Vargas, J Barba-León, J Vázquez-Navarrete, J Acosta-Dibarrat, C Salgado-Miranda
AIMS: The objective of this study was to obtain a phenotypic and genotypic profile of Salmonella enterica including multidrug-resistant isolates from food-producing animals and clinical isolates, as well as their genetic relatedness in two different States of Mexico (Jalisco and State of Mexico). METHODS AND RESULTS: A total of 243 isolates were evaluated in terms of antimicrobial resistance and related genes through a disk diffusion method and PCR respectively; we found sixteen multidrug-resistant isolates, all of them harbouring the blaCMY gene but not qnr genes, these isolates represent less than 10% of the collection...
October 17, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29044946/aquaporin-1-inhibition-reduces-metastatic-formation-in-a-mouse-model-of-melanoma
#13
Laura Simone, Concetta Domenica Gargano, Francesco Pisani, Antonio Cibelli, Maria Grazia Mola, Antonio Frigeri, Maria Svelto, Grazia Paola Nicchia
Aquaporin-1 (AQP1) is a proangiogenic water channel protein promoting endothelial cell migration. We previously reported that AQP1 silencing by RNA interference reduces angiogenesis-dependent primary tumour growth in a mouse model of melanoma. In this study, we tested the hypothesis that AQP1 inhibition also affects animal survival and lung nodule formation. Melanoma was induced by injecting B16F10 cells into the back of C57BL6J mice. Intratumoural injection of AQP1 siRNA and CTRL siRNA was performed 10 days after tumour cell implantation...
October 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29044850/mesenchymal-stem-cells-therapy-a-promising-cell-based-therapy-for-treatment-of-myocardial-infraction
#14
REVIEW
Ayman El Sayed Shafei, Mahmoud Ahmed Ali, Hazem G Ghanem, Ahmed I Shehata, Ahmed A Abdelgawad, Hossam R Handal, Kareem A Talaat, Ahmed E Ashaal, Amal S El-Shal
AIM: For decades, mesenchymal stem (MSCs) cells had been used for cardiovascular diseases as regenerative therapy. This review is an attempt to summarize the types of MSCs involved in MI therapy, its possible mechanisms effects especially paracrine one in MI focusing on the studies (human and animal) conducted in the last 10 years. DISCUSSION: Recently, reports showed that MSC therapy could have infarct-limiting effects after myocardial infarction (MI) in both experimental and clinical trials...
October 16, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29044447/relationship-between-androgen-deficiency-and-memory-impairment-in-aging-and-alzheimer-8217-s-disease
#15
Graciela Jiménez-Rubio, José J Herrera-Pérez, Olivia T Hernández-Hernández, Lucía Martínez-Mota
Aging and Alzheimer’s disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a greater participation of neurofibrillary tangles (NFTs) than that of senile plaques, as responsible for cognitive impairment in AD and normal aging. On the other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies give evidence that hypoandrogenism is associated with memory impairment...
September 2017: Actas Españolas de Psiquiatría
https://www.readbyqxmd.com/read/29043083/a-framework-for-continuous-target-tracking-during-mr-guided-high-intensity-focused-ultrasound-thermal-ablations-in-the-abdomen
#16
Cornel Zachiu, Baudouin Denis de Senneville, Ivan D Dmitriev, Chrit T W Moonen, Mario Ries
BACKGROUND: During lengthy magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU) thermal ablations in abdominal organs, the therapeutic work-flow is frequently hampered by various types of physiological motion occurring at different time-scales. If left un-addressed this can lead to an incomplete therapy and/or to tissue damage of organs-at-risk. While previous studies focus on correction schemes for displacements occurring at a particular time-scale within the work-flow of an MRg-HIFU therapy, in the current work we propose a motion correction strategy encompassing the entire work-flow...
2017: Journal of Therapeutic Ultrasound
https://www.readbyqxmd.com/read/29042035/a-systematic-review-of-molecular-responses-to-cancer-therapy-in-normal-human-mucosa
#17
REVIEW
Mette Marcussen, Conni Skrubbeltrang, Julie Støve Bødker, Ilse Christiansen, Martin Bøgsted, Karen Dybkær, Olav Jonas Bergmann, Hans Erik Johnsen
OBJECTIVE: Cancer therapy-induced inflammation of oral and gastrointestinal mucosae affects patients nonuniformly. Preventive strategies are limited; no biomarker exists for pretreatment identification of patients likely to be severely affected. Animal models are preferred for studying molecular responses in mucosae during chemotherapy, but translation into clinical practice is difficult. We performed a systematic review to retrieve articles that described molecular changes in human mucosae during cancer therapy...
October 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29042028/importance-of-the-leukotriene-b4-blt1-and-ltb4-blt2-pathways-in-asthma
#18
REVIEW
Erwin W Gelfand
For several decades, the leukotriene pathways have been implicated as playing a central role in the pathophysiology of asthma. The presence and elevation of numerous metabolites in the blood, sputum, and bronchoalveolar lavage fluid from asthmatics or experimental animals adds support to this notion. However, targeting of the leukotriene pathways has had, in general, limited success. The single exception in asthma therapy has been targeting of the cysteinyl leukotriene receptor 1, which clinically has proven effective but only in certain clinical situations...
October 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/29042014/effects-of-cathelicidin-derived-peptide-from-reptiles-on-lipopolysaccharide-induced-intestinal-inflammation-in-weaned-piglets
#19
Haiwen Zhang, Bingxi Zhang, Xiaomeng Zhang, Xuemei Wang, Kebang Wu, Qingfeng Guan
Cathelicidins are the largest family of antimicrobial peptides. C-BF, which is short for Cathelicidin-Bungarus Fasciatus, was isolated from snake venom. C-BF was found to be the most potential substitutes for antibiotics. In this study, we analyzed the effects of cathelicidin-derived peptide C-BF, on lipopolysaccharide (LPS)-induced intestinal damage in weaned piglets, to evaluate the therapeutic effect of C-BF on infectious disease of piglets. Twenty-four piglets were randomly assigned into four groups: control, C-BF, LPS, and C-BF+LPS...
October 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29041961/treatment-evaluation-of-wharton-s-jelly-derived-mesenchymal-stem-cells-using-a-chronic-salpingitis-model-an-animal-experiment
#20
Zhe Li, Zhao Zhang, Xin Chen, Juan Zhou, Xiao-Min Xiao
BACKGROUND: The present study was conducted to evaluate new methods to repair the reproductive function of the oviduct, thereby allowing gametes to combine and grow in vivo under natural circumstances. METHODS: Sixty pathogen-free female New Zealand rabbits were divided into three groups: a wild-type group, an untreated control group, and a treatment group. Disposable sterile newborn sputum suction tubes were inserted into the urogenital tract to instill an Escherichia coli suspension into the uterine cavity to establish the chronic salpingitis model...
October 17, 2017: Stem Cell Research & Therapy
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