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https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#1
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088634/chitosan-g-poly-n-isopropylacrylamide-copolymers-as-delivery-carriers-for-intracameral-pilocarpine-administration
#2
Jui-Yang Lai, Li-Jyuan Luo
This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088517/osborne-mendel-rats-simultaneously-develop-cardiac-and-renal-dysfunction-left-atrial-thrombosis-peripheral-artery-occlusion-and-ascending-aortic-dissection
#3
Makoto Asahina, Hideki Matsumoto, Yoshitaka Yasuhara, Noriko Suzuki, Ritsuko Takami, Michiyasu Takeyama, Ryuichi Tozawa
Although chronic kidney disease (CKD) is strongly associated with onsets of cardiovascular disease (CVD), the pathogenic mechanism between these diseases has not been fully understood. To develop and validate new therapeutic strategies for this complication, appropriate experimental models that reflect the complexity of the underlying pathophysiology are needed. The Osborne-Mendel (OM) rat was identified as an atherosclerosis-prone and a premature-death rat strain among 16 inbred rat strains when fed high-cholesterol containing diet...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088487/adenosine-receptors-and-caffeine-in-retinopathy-of-prematurity
#4
REVIEW
Jiang-Fan Chen, Shuya Zhang, Rong Zhou, Zhenlang Lin, Xiaohong Cai, Jing Lin, Yuqin Huo, Xiaoling Liu
Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants...
January 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28088382/functional-electrical-stimulation-for-foot-drop-in-multiple-sclerosis-a-systematic-review-and-meta-analysis-of-the-impact-on-gait-speed
#5
REVIEW
Linda Miller, Angus McFadyen, Anna C Lord, Rebecca Hunter, Lorna Paul, Danny Rafferty, Roy Bowers, Paul Mattison
OBJECTIVE: To review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests. DATA SOURCES: Five databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched. STUDY SELECTION: Studies of both observational and experimental design where gait speed data in pwMS could be extracted were included...
January 11, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#6
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#7
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28086912/wwl70-attenuates-pge2-production-derived-from-2-arachidonoylglycerol-in-microglia-by-abhd6-independent-mechanism
#8
Mikiei Tanaka, Sean Moran, Jie Wen, Kwame Affram, Tinghua Chen, Aviva J Symes, Yumin Zhang
BACKGROUND: α/β-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia...
January 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28079810/risk-of-vertebral-compression-fractures-in-multiple-myeloma-patients-a-finite-element-study
#9
D Anitha, Baum Thomas, Kirschke S Jan, Karupppasamy Subburaj
The purpose of this study was to develop and validate a finite element (FE) model to predict vertebral bone strength in vitro using multidetector computed tomography (MDCT) images in multiple myeloma (MM) patients, to serve as a complementing tool to assess fracture risk. In addition, it also aims to differentiate MM patients with and without vertebral compression fractures (VCFs) by performing FE analysis on vertebra segments (T1-L5) obtained from in vivo routine MDCT imaging scans. MDCT-based FE models were developed from the in vitro vertebrae samples and were then applied to the in vivo vertebrae segments of MM patients (n = 4) after validation...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079600/acute-administration-of-cyclosporine-a-does-not-impair-attention-or-memory-performance-in-healthy-men
#10
Anna L Kahl, Julia Kirchhof, Anna Füting, Bernd-Otto Hütter, Benjamin Wilde, Oliver Witzke, Sven Benson, Martin Hadamitzky, Manfred Schedlowski
There is clinical and experimental evidence that treatment with immunosuppressive and antiproliferative drugs such as the calcineurin inhibitor cyclosporine A (CsA) is associated with mental health problems and neuropsychological disturbances in patients. However, it remains unclear whether and to what extent cognitive functions such as memory and attention processes are affected by the pharmacological treatment. This is partly because of the fact that it is difficult to refer the observed neuropsychological disturbances in patients to the drug itself, to drug-induced immune suppression, or to interaction with other medication or comorbidities...
January 11, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28077981/dna-polymerase-kappa-protects-human-cells-against-mmc-induced-genotoxicity-through-error-free-translesion-dna-synthesis
#11
Yuki Kanemaru, Tetsuya Suzuki, Akira Sassa, Kyomu Matsumoto, Noritaka Adachi, Masamitsu Honma, Satoshi Numazawa, Takehiko Nohmi
BACKGROUND: Interactions between genes and environment are critical factors for causing cancer in humans. The genotoxicity of environmental chemicals can be enhanced via the modulation of susceptible genes in host human cells. DNA polymerase kappa (Pol κ) is a specialized DNA polymerase that plays an important role in DNA damage tolerance through translesion DNA synthesis. To better understand the protective roles of Pol κ, we previously engineered two human cell lines either deficient in expression of Pol κ (KO) or expressing catalytically dead Pol κ (CD) in Nalm-6-MSH+ cells and examined cytotoxic sensitivity against various genotoxins...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28077784/identification-and-characterization-of-hpv-independent-cervical-cancers
#12
Carolyn E Banister, Changlong Liu, Lucia Pirisi, Kim E Creek, Phillip J Buckhaults
BACKGROUND: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077675/post-hoc-assessment-of-the-immunogenicity-of-bioengineered-factor-viia-demonstrates-the-use-of-preclinical-tools
#13
Kasper Lamberth, Stine Louise Reedtz-Runge, Jonathan Simon, Ksenia Klementyeva, Gouri Shankar Pandey, Søren Berg Padkjær, Véronique Pascal, Ileana R León, Charlotte Nini Gudme, Søren Buus, Zuben E Sauna
Immunogenicity is an important consideration in the licensure of a therapeutic protein because the development of neutralizing anti-drug antibodies (ADAs) can affect both safety and efficacy. Neoantigens introduced by bioengineering of a protein drug are a particular cause for concern. The development of a bioengineered recombinant factor VIIa (rFVIIa) analog was discontinued after phase 3 trials because of the development of ADAs. The unmodified parent molecule (rFVIIa), on the other hand, has been successfully used as a drug for more than two decades with no reports of immunogenicity in congenital hemophilia patients with inhibitors...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077318/alcohol-microbiome-life-style-influence-alcohol-and-non-alcoholic-organ-damage
#14
REVIEW
Manuela G Neuman, Samuel W French, Samir Zakhari, Stefen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, onJune 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealedthe basic aspects of alcohol metabolism that may be responsible for the development of liver diseaseas well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28077215/analyzing-therapeutic-change-using-modified-brinley-plots-history-construction-and-interpretation
#15
Neville M Blampied
The paper reviews the history, construction, and interpretation of modified Brinley plots, a scatter plot used in therapy outcome research to compare each individual participant's scores on the same dependent variable at Time 1 (normally pretreatment baseline; x-axis), with scores at selected times during or after treatment (y-axis). Since 1965 eponymously named Brinley plots have occasionally been used in experimental psychology to display group mean data. Between 1979 and 1995 a number of clinical researchers modified Brinley plots to show individuals' data but these plots have received little subsequent use...
January 2017: Behavior Therapy
https://www.readbyqxmd.com/read/28075453/mir-375-inhibits-cancer-stem-cell-phenotype-and-tamoxifen-resistance-by-degrading-hoxb3-in-human-er-positive-breast-cancer
#16
Hui Fu, Lei Fu, Chao Xie, Wen-Shu Zuo, Yan-Song Liu, Mei-Zhu Zheng, Jin-Ming Yu
Cancer stem cell (CSC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in tumor cell invasion and metastasis. They have been shown to occur in resistance to tamoxifen. Moreover, microRNAs (miRNAs) have been associated with CSCs, EMT as well as tamoxifen resistance. Studying molecular mechanism of CSCs, EMT as well as tamoxifen resistance will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that miR-375 inhibits CSC traits in breast cancer MCF-7 cells...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074906/antiproliferative-effects-of-1%C3%AE-oh-vitd3-in-malignant-melanoma-potential-therapeutic-implications
#17
Lucia Spath, Alessandra Ulivieri, Luca Lavra, Laura Fidanza, Marta Carlesimo, Maria Giubettini, Alessandra Narcisi, Emidio Luciani, Barbara Bucci, Daniela Pisani, Salvatore Sciacchitano, Armando Bartolazzi
Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow's thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074716/semiquantitative-immunohistochemical-detection-of-progesterone-receptors-in-male-accessory-sex-glands-as-a-screening-assay-for-anabolic-steroid-use-in-bulls
#18
Claudia Zanardello, Katia Capello, Roberto Stella, Giancarlo Biancotto, Marta Vascellari
We investigated the immunohistochemical expression of progesterone receptors (PRs) in the prostate and bulbourethral glands of thirty-two 10-14-mo-old Charolais bulls following treatment with a low dosage of estrogens. Animals were divided into 2 groups: 16 animals (group T) were treated for 71 d with a therapeutic dose of trenbolone acetate and estradiol by subcutaneous implant, 16 animals (group C) received no treatment. Urine samples were collected both at the beginning of the trial and 9 times during the study...
January 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28074663/primary-graft-dysfunction-pathophysiology-to-guide-new-preventive-therapies
#19
Ciara M Shaver, Lorraine B Ware
Primary graft dysfunction (PGD) is a common complication of lung transplantation characterized by acute pulmonary edema associated with bilateral pulmonary infiltrates and hypoxemia in the first 3 post-operative days. Development of PGD is a predictor of poor short- and long-term outcomes after lung transplantation, but there are currently limited tools to prevent its occurrence. Areas covered: Several potentially modifiable donor, recipient, and operative risk factors for PGD have been identified. In addition, basic and translational studies in animals and ex vivo lung perfusion systems have identified several biomarkers and mechanisms of injury in PGD...
January 11, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28074475/what-makes-you-feel-sick-after-inflammation-predictors-of-acute-and-persisting-physical-sickness-symptoms-induced-by-experimental-endotoxemia
#20
Sven Benson, Harald Engler, Alexander Wegner, Laura Rebernik, Ingo Spreitzer, Manfred Schedlowski, Sigrid Elsenbruch
We aimed to identify statistical predictor variables of LPS-induced physical sickness symptoms during the acute and late inflammatory phases using multivariate regression analyses. Data from N=128 healthy volunteers who received i.v. LPS injection (0.4 or 0.8 ng/kg) or placebo were pooled for analyses. Physical sickness symptoms experienced during the acute (0-6h post-injection) and late (6-24h post-injection) phases were assessed with the validated General-Assessment-of-Side-Effects (GASE) questionnaire. LPS-treated subjects reported significantly more physical sickness symptoms...
January 11, 2017: Clinical Pharmacology and Therapeutics
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