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https://www.readbyqxmd.com/read/29331959/probenecid-improves-cardiac-function-in-patients-with-heart-failure-with-reduced-ejection-fraction-in-vivo-and-cardiomyocyte-calcium-sensitivity-in-vitro
#1
Nathan Robbins, Mark Gilbert, Mohit Kumar, James W McNamara, Patrick Daly, Sheryl E Koch, Ginger Conway, Mohamed Effat, Jessica G Woo, Sakthivel Sadayappan, Jack Rubinstein
BACKGROUND: Transient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration-approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium-dependent effects on myocyte contractility...
January 13, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#2
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331789/anticonvulsant-activities-of-%C3%AE-asaronol-e-3-hydroxyasarone-an-active-constituent-derived-from-%C3%AE-asarone
#3
Xirui He, Yajun Bai, Min Zeng, Zefeng Zhao, Qiang Zhang, Ning Xu, Fanggang Qin, Xiaoyang Wei, Meimei Zhao, Ni Wu, Zehua Li, Yajun Zhang, Tai-Ping Fan, Xiaohui Zheng
BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice...
August 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29331765/5-6-dihydropyrimidine-1-2h-carbothioamides-synthesis-in-vitro-gaba-at-screening-anticonvulsant-activity-and-molecular-modelling-study
#4
Meeta Sahu, Nadeem Siddiqui, Vidushi Sharma, Sharad Wakode
Even after considerable advances in the field of epilepsy treatment, convulsions are inefficiently controlled by standard drug therapy. Herein, a series of pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant agents by doing some important structural modifications in well-known anticonvulsant drugs. Two classical animal models were used for the in vivo anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod method...
January 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29331677/identification-of-potential-mr-derived-biomarkers-for-tumor-tissue-response-to-177lu-octreotate-therapy-in-an-animal-model-of-small-intestine-neuroendocrine-tumor
#5
Mikael Montelius, Johan Spetz, Oscar Jalnefjord, Evelin Berger, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy response assessment, but associations between MR parameters, underlying biology, and therapeutic effects must be investigated. The aim of this study was to investigate response assessment efficacy and biological associations of MR parameters in a neuroendocrine tumor (NET) model subjected to radionuclide treatment. Twenty-one mice with NETs received 177Lu-octreotate at day 0. MR experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements (T1/T2*)...
January 10, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29331041/effect-of-low-level-laser-therapy-on-the-healing-of-sites-grafted-with-coagulum-deproteinized-bovine-bone-and-biphasic-ceramic-made-of-hydroxyapatite-and-%C3%AE-tricalcium-phosphate-in-vivo-study-in-rats
#6
Guilherme J P L de Oliveira, Maurício A T Aroni, Marcell C Medeiros, Elcio Marcantonio, Rosemary A C Marcantonio
OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) on the healing of biomaterial graft areas (i.e., coagulum, deproteinized bovine bone, and biphasic ceramics comprising hydroxyapatite and β-tricalcium phosphate). MATERIAL AND METHODS: Ninety rats were divided into two groups according to laser irradiation use (λ 808 nm, 100 mW, φ ∼600 μm, seven sessions with 28 J of irradiation dose in total): a laser group and a control group...
January 13, 2018: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29330880/concise-review-optimized-strategies-for-stem-cell-based-therapy-in-myocardial-repair-clinical-translatability-and-potential-limitation
#7
REVIEW
Rongrong Wu, Xinyang Hu, Jian'an Wang
Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects...
January 13, 2018: Stem Cells
https://www.readbyqxmd.com/read/29330870/cell-therapy-for-spinal-cord-injury-with-olfactory-ensheathing-glia-cells-oecs
#8
REVIEW
Rosa M Gómez, Magdy Y Sánchez, Maria Portela-Lomba, Kemel Ghotme, George E Barreto, Javier Sierra, M Teresa Moreno-Flores
The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs)...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#9
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330709/in-vitro-and-in-vivo-activity-of-iclaprim-a-diaminopyrimidine-compound-and-potential-therapeutic-alternative-against-pneumocystis-pneumonia
#10
E M Aliouat, E Dei-Cas, N Gantois, M Pottier, C Pinçon, S Hawser, A Lier, D B Huang
Pneumocystis pneumonia is a serious complication that may affect immunosuppressed patients. The absence of reliable and safe therapeutic alternatives to trimethoprim-sulfamethoxazole (TMP/SMX) justifies the search for more effective and less toxic agents. In this study, the in vitro and in vivo anti-Pneumocystis jirovecii activity of iclaprim, a diaminopyrimidine compound that exerts its antimicrobial activity through the inhibition of dihydrofolate reductase (DHFR), as does TMP, was evaluated alone or in combination with SMX...
January 12, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29330473/endothelial-heparan-sulfate-deficiency-reduces-inflammation-and-fibrosis-in-murine-diabetic-nephropathy
#11
Ditmer T Talsma, Kirankumar Katta, Marieke A B Ettema, Berna Kel, Marion Kusche-Gullberg, Moh R Daha, Coen A Stegeman, Jacob van den Born, Lianchun Wang
Inflammation plays a vital role in the development of diabetic nephropathy, but the underlying regulatory mechanisms are only partially understood. Our previous studies demonstrated that, during acute inflammation, endothelial heparan sulfate (HS) contributes to the adhesion and transendothelial migration of leukocytes into perivascular tissues by direct interaction with L-selectin and the presentation of bound chemokines. In the current study, we aimed to assess the role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic nephropathy mouse model...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29329623/parasite-control-strategies-used-by-equine-owners-in-the-united-states-a-national-survey
#12
M K Nielsen, M A Branan, A M Wiedenheft, R Digianantonio, L P Garber, C A Kopral, A M Phillippi-Taylor, J L Traub-Dargatz
The widespread occurrence of anthelmintic resistance in equine parasites across the world has led to recommendations of fecal egg count-based parasite programs to reduce treatment intensity and thereby delay further development of resistance as much as possible. The most recent study describing equine parasite control in the United States was conducted 20 years ago, and little is known about current strategies employed. This study was part of the National Animal Health Monitoring Systems (NAHMS) Equine 2015 Study, and aimed to describe equine parasite control strategies in the U...
January 30, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29329593/targeting-ectodysplasin-promotor-by-crispr-dcas9-effector-effectively-induces-the-reprogramming-of-human-bone-marrow-derived-mesenchymal-stem-cells-into-sweat-gland-like-cells
#13
Sujing Sun, Jun Xiao, Jiahui Huo, Zhijun Geng, Kui Ma, Xiaoyan Sun, Xiaobing Fu
BACKGROUND: Patients with a deep burn injury are characterized by losing the function of perspiration and being unable to regenerate the sweat glands. Because of their easy accession, multipotency, and lower immunogenicity, bone marrow-derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source for cell therapy. The aim of this study was to identify whether targeting the promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce the BM-MSCs to differentiate into sweat gland-like cells (SGCs)...
January 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29329020/a-novel-mouse-model-of-atopic-dermatitis-that-is-t-helper-2-th2-polarized-by-an-epicutaneous-allergen
#14
Hyun Jung Park, Wahn Soo Choi, Won Young Lee, Youngsok Choi, Chankyu Park, Jin Hoi Kim, Kwon Ho Hong, Hyuk Song
The pathogenesis of atopic dermatitis (AD) involves T helper 2 (Th2) cells, and effective therapies remain elusive due to the paucity of animal models. We aimed to develop a mouse model of an immune system aberration caused by allergen. Experiments were conducted in two phases. In experiment 1, BALB/c mice were sensitized with one of four chemical allergens - toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), trimellitic anhydride (TMA), or 2,4-dinitrochlorobenzene (DNCB) - for 3 weeks. Based on results of experiment 1, immunological features were compared between TMA-sensitized BALB/c mice and NC/Nga mice, after exposure to mite extracts, harmful chemicals and detergents in experiment 2...
December 29, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29328364/genetically%C3%A2-modified-stem-cells-in-treatment-of-human-diseases-tissue-kallikrein-klk1-%C3%A2-based-targeted-therapy-review
#15
Marina Devetzi, Maria Goulielmaki, Nicolas Khoury, Demetrios A Spandidos, Georgia Sotiropoulou, Ioannis Christodoulou, Vassilis Zoumpourlis
The tissue kallikrein‑kinin system (KKS) is an endogenous multiprotein metabolic cascade which is implicated in the homeostasis of the cardiovascular, renal and central nervous system. Human tissue kallikrein (KLK1) is a serine protease, component of the KKS that has been demonstrated to exert pleiotropic beneficial effects in protection from tissue injury through its anti‑inflammatory, anti‑apoptotic, anti‑fibrotic and anti‑oxidative actions. Mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) constitute populations of well‑characterized, readily obtainable multipotent cells with special immunomodulatory, migratory and paracrine properties rendering them appealing potential therapeutics in experimental animal models of various diseases...
January 3, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29328070/nerve-growth-factor-upregulates-sirtuin-1-expression-in-cholestasis-a-potential-therapeutic-target
#16
Ming-Shian Tsai, Po-Huang Lee, Cheuk-Kwan Sun, Ting-Chia Chiu, Yu-Chun Lin, I-Wei Chang, Po-Han Chen, Ying-Hsien Kao
This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29327941/infection-is-not-required-for-mucoinflammatory-lung-disease-in-cftr-knockout-ferrets
#17
Bradley H Rosen, T Idil Apak Evans, Shashanna R Moll, Jaimie S Gray, Bo Liang, Xingshen Sun, Yulong Zhang, Chandler W Jensen-Cody, Anthony M Swatek, Weihong Zhou, Nan He, Pavana G Rotti, Scott R Tyler, Nicholas W Keiser, Preston J Anderson, Leonard Brooks, Yalan Li, R Marshall Pope, Maheen Rajput, Eric A Hoffman, Kai Wang, J Kirk Harris, Kalpaj R Parekh, Katherine N Gibson-Corley, John F Engelhardt
RATIONALE: Classical interpretation of cystic fibrosis (CF) lung disease pathogenesis suggests that infection initiates disease progression, leading to an exuberant inflammatory response, excessive mucus, and ultimately bronchiectasis. While symptomatic antibiotic treatment controls lung infections early in disease, life-long bacterial residence typically ensues. Processes that control the establishment of persistent bacteria in the CF lung, and the contribution of non-infectious components to disease pathogenesis, are poorly understood...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29326851/recent-advancements-in-gene-therapy-for-hereditary-retinal-dystrophies
#18
REVIEW
Ayşe Öner
Hereditary retinal dystrophies (HRDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision, and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles, with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family, highlighting further levels of complexity...
December 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/29326144/a-new-secretory-peptide-of-natriuretic-peptide-family-osteocrin-suppresses-the-progression-of-congestive-heart-failure-after-myocardial-infarction
#19
Takahiro Miyazaki, Kentaro Otani, Ayano Chiba, Hirohito Nishimura, Takeshi Tokudome, Haruko Watanabe-Takano, Ayaka Matsuo, Hiroyuki Ishikawa, Keiko Shimamoto, Hajime Fukui, Yugo Kanai, Akihiro Yasoda, Soshiro Ogata, Kunihiro Nishimura, Naoto Minamino, Naoki Mochizuki
Rationale: An increase of severe ischemic heart diseases results in an increase of the patients with congestive heart failure (CHF). Therefore, new therapies are expected in addition to recanalization of coronary arteries. Previous clinical trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs. Objective: We aimed at investigating whether osteocrin (OSTN) peptide potentially functioning as an NP clearance receptor (NPR3)-blocking peptide can be used as a new therapeutic peptide for treating CHF after myocardial infarction (MI) using animal models...
January 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29325489/creating-effective-biocontainment-facilities-and-maintenance-protocols-for-raising-specific-pathogen-free-severe-combined-immunodeficient-scid-pigs
#20
Ellis J Powell, Sara Charley, Adeline N Boettcher, Lisa Varley, Justin Brown, Martine Schroyen, Malavika K Adur, Susan Dekkers, Dean Isaacson, Mary Sauer, Joan Cunnick, N Matthew Ellinwood, Jason W Ross, Jack Cm Dekkers, Christopher K Tuggle
Severe combined immunodeficiency (SCID) is defined by the lack of an adaptive immune system. Mutations causing SCID are found naturally in humans, mice, horses, dogs, and recently in pigs, with the serendipitous discovery of the Iowa State University SCID pigs. As research models, SCID animals are naturally tolerant of xenotransplantation and offer valuable insight into research areas such as regenerative medicine, cancer therapy, as well as immune cell signaling mechanisms. Large-animal biomedical models, particularly pigs, are increasingly essential to advance the efficacy and safety of novel regenerative therapies on human disease...
January 1, 2018: Laboratory Animals
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