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Experimental therapeutics

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https://www.readbyqxmd.com/read/28636995/experimental-study-on-the-therapeutic-effect-and-underlining-mechanisms-of-positron-in-pancreatic-cancer-cells
#1
Ying Wang, Ming Li, Rao Diao, Brian Tung, Dalong Zhang, Yaming Li
The purpose of this study was to assess the potential therapeutic effect of positrons emitted by 18F-2-Deoxy-2-Fluoro-D-Glucose (18F-FDG) on pancreatic cancer cells and elucidate its underlying mechanisms. Pancreatic cancer cells were incubated with different radioactive concentrations of 18F-FDG and evaluated for anti-cancer properties and underlining mechanisms. In addition, three groups of tumor-bearing mice were treated with different doses of 18F-FDG weekly, the tumor growth rate was calculated, and the mice were imaged by positron emission tomography (PET) with 18F-FDG before and after treatment...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#2
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636950/structural-evidence-of-quercetin-multi-target-bioactivity-a-reverse-virtual-screening-strategy
#3
Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J Williams, Juan A Abin-Carriquiry
The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways...
June 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28636542/niaoduqing-granules-relieve-chronic-kidney-disease-symptoms-by-decreasing-renal-fibrosis-and-anemia
#4
Xu Wang, Suyun Yu, Qi Jia, Lichuan Chen, Jinqiu Zhong, Yanhong Pan, Peiliang Shen, Yin Shen, Siliang Wang, Zhonghong Wei, Yuzhu Cao, Yin Lu
NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#5
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636047/decoding-the-regulatory-mechanism-of-glucose-and-insulin-induced-phosphatidylinositol-3-4-5-trisphosphate-dynamics-in-%C3%AE-cells
#6
Tagari Samanta, Peeyush Sharma, Dwijendra Kukri, Sandip Kar
In MIN6 pancreatic β-cells, glucose and insulin act in a synergistic manner to regulate the dynamics of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the precise regulatory mechanism behind such an experimentally observed synergy is poorly understood. In this article, we propose a phenomenological mathematical model for studying the glucose and insulin driven PIP3 activation dynamics under various stimulatory conditions to unfold the mechanism responsible for the observed synergy. The modeling study reveals that the experimentally observed oscillation in PIP3 dynamics with disparate time scales for different external glucose doses is mainly orchestrated by the complex dynamic regulation of cytosolic Ca(2+) in β-cells...
June 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28635608/the-protective-role-of-folic-acid-against-testicular-dysfunction-in-lead-intoxicated-rat-model
#7
Asmaa Ms Gomaa, Nasser S Abou Khalil, Mohammed A Abdel-Ghani
There is an increasing concern over male reproductive toxicity caused by lead exposure. Folic acid (FA) is supposed to be a promising therapeutic strategy against lead toxicity. Therefore, the aim of this experimental study was to shed light on the potential protective role of FA on lead-induced testicular dysfunction in rats and its possible underlying mechanistic pathways. Rats (n = 24) were divided into four groups: Control, FA, Lead, and FA+Lead group. After 4 weeks, lead intoxication resulted in a marked reduction in the relative testicular weight and the serum level of testosterone, an impairment in the characters of semen analysis, and an increased content of lead, malondialdehyde and both interleukin-6 and -10 and a decreased antioxidant enzyme levels in the testicular tissue homogenate...
July 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/28635514/effects-of-thyroid-hormone-therapy-on-cut-surface-healing-of-the-remnant-stomach-with-short-term-weight-loss-alterations-after-sleeve-gastrectomy
#8
Suleyman Orman, Kerem Karaman, Banu Isbilen Basok, Ucler Kisa, Ayse Bahar Ceyran, Erdal Birol Bostanci
BACKGROUND: The hypothalamic-pituitary-tyhroid axis is directly affected by drastic changes in energy stores. The aim of the present study was to determine the effects of triiodothyronine (T3) treatment on cut-surface healing of remnant stomach with weight loss alterations after sleeve gastrectomy (SG). METHODS: Thirty male Wistar Albino rats were divided into three groups: sham (n = 6), control (n = 12), and experimental (n = 12). Control and experimental group rats underwent sleeve gastrectomy...
February 16, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28635328/dietary-implications-for-patients-receiving-long-term-oral-anticoagulation-therapy-for-treatment-and-prevention-of-thromboembolic-disease
#9
Emmanouela Kampouraki, Farhad Kamali
The effectiveness of oral anticoagulation therapy with warfarin (a vitamin K antagonist) in the treatment of thromboembolic disease, including stroke prophylaxis in patients with atrial fibrillation is well recognised. However, warfarin has a narrow therapeutic window and an unpredictable anticoagulation response, which make it difficult to achieve and maintain optimal anticoagulation. Various dietary factors, including sudden changes in eating patterns, can significantly alter anticoagulation control, thereby potentially exposing patients to the risk of bleeding or thromboembolic complications...
June 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28635176/genetic-loss-of-the-muscarinic-m3-receptor-m3-r-markedly-alters-bile-formation-and-cholestatic-liver-injury-in-mice
#10
Franziska Durchschein, Elisabeth Krones, Marion J Pollheimer, Gernot Zollner, Martin Wagner, Jean-Pierre Raufman, Peter Fickert
Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. We compared bile flow and composition in M3 -R knock-out mice (M3 -R(-/-) ) and wild type littermates (WT). M3 -R(-/-) mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3(-) secretion...
June 21, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28634590/the-immune-epitope-database-how-data-are-entered-and-retrieved
#11
REVIEW
Ward Fleri, Kerrie Vaughan, Nima Salimi, Randi Vita, Bjoern Peters, Alessandro Sette
Easy access to a vast collection of experimental data on immune epitopes can greatly facilitate the development of therapeutics and vaccines. The Immune Epitope Database and Analysis Resource (IEDB) was developed to provide such a resource as a free service to the biomedical research community. The IEDB contains epitope and assay information related to infectious diseases, autoimmune diseases, allergic diseases, and transplant/alloantigens for humans, nonhuman primates, mice, and any other species studied. It contains T cell, B cell, MHC binding, and MHC ligand elution experiments...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634441/roles-of-pannexin-1-channels-in-inflammatory-response-through-the-tlrs-nf-kappa-b-signaling-pathway-following-experimental-subarachnoid-hemorrhage-in-rats
#12
Ling-Yun Wu, Zhen-Nan Ye, Chen-Hui Zhou, Chun-Xi Wang, Guang-Bin Xie, Xiang-Sheng Zhang, Yong-Yue Gao, Zi-Huan Zhang, Meng-Liang Zhou, Zong Zhuang, Jing-Peng Liu, Chun-Hua Hang, Ji-Xin Shi
Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28634361/uridine-ameliorates-dextran-sulfate-sodium-dss-induced-colitis-in-mice
#13
Manish Kumar Jeengar, Dinesh Thummuri, Mattias Magnusson, V G M Naidu, Srinivas Uppugunduri
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#14
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28633982/corrigendum-to-does-size-and-site-matter-in-therapeutic-decompressive-craniectomy-a-laboratory-based-experimental-study-world-neurosurgery-95-2016-441-446
#15
Kate Millar, Sam Eljamel
No abstract text is available yet for this article.
June 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28632743/in-silico-assessment-of-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-1-in-the-human-ventricles
#16
Cunjin Luo, Kuanquan Wang, Henggui Zhang
AIMS: Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1...
2017: PloS One
https://www.readbyqxmd.com/read/28631902/-comparative-estimation-of-antilithogenic-activity-of-porcine-kidney-derived-biomedical-substance-and-sodium-citrate-in-experimental-urolithiasis
#17
G V Pavlyashik, A Yu Zharikov, V I Kiselev
AIM: to compare the anti-lithogenic activity of biomedical substance derived from freeze-dried porcine kidney and sodium citrate. MATERIALS AND METHODS: The experiments were conducted on Wistar rats divided into three groups of 15 animals each: control group (disease control), comparison group (sodium citrate treatment) and experimental group (treatment with biomedical substance from porcine kidneys). Experimental urolithiasis was modeled using the ethylene glycol model...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28631556/kruppel-like-factor-4-inhibits-non-small-cell-lung-cancer-cell-growth-and-aggressiveness-by-stimulating-transforming-growth-factor-%C3%AE-1-meidated-erk-jnk-nf-%C3%AE%C2%BAb-signaling-pathways
#18
Renzhi Yu, Lei Han, Xin Ni, Minghuan Wang, Ping Xue, Li Zhang, Mei Yuan
Non-small cell lung cancer is one of the most common epithelial tumors that cause the most common cancer-related mortality due to invasive ability. Research has found that Kruppel-like factor 4, a zinc-finger transcription factor, plays a critical role in the tumor evolution and progression. However, the molecular signal pathways mediated by Kruppel-like factor 4 in the progression of non-small cell lung cancer cells have not been well understood yet. In this study, we investigated the possible role and potential mechanism of Kruppel-like factor 4 in growth and aggressiveness of non-small cell lung cancer cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631484/ocular-pharmacokinetics-of-therapeutic-antibodies-given-by-intravitreal-injection-estimation-of-retinal-permeabilities-using-a-3-compartment-semi-mechanistic-model
#19
Laurence A Hutton-Smith, Eamonn A Gaffney, Helen M Byrne, Philip K Maini, Kapil Gadkar, Norman Alan Mazer
Intravitreally (IVT) injected macromolecules for the treatment of age-related macular degeneration must permeate through the inner limiting membrane (ILM) into the retina and through the retinal pigment epithelium (RPE) to enter the choroid. A quantitative understanding of intraocular transport mechanisms, elimination pathways and the effect of molecular size, is currently incomplete. We present a semi-mechanistic, 3-compartment (retina, vitreous and aqueous) pharmacokinetic (PK) model, expressed using linear ordinary differential equations (ODEs), to describe the molecular concentrations following a single IVT injection...
June 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28631311/the-il-10-stat3-axis-contributions-to-immune-tolerance-by-thymus-and-peripherally-derived-regulatory-t-cells
#20
REVIEW
Klaus G Schmetterer, Winfried F Pickl
The signal transducer and activator of transcription (STAT) proteins are important mediators for the integration of extrinsic signals provided by cytokines and hormones and thereby adapt cellular processes to their surroundings. In the past decade, the involvement of STAT3 in the regulation of T-cell responses has become a topic of increasing interest. STAT3 is activated in response to multiple cytokines, many of which have been shown to influence T-cell responses. Interestingly, many of these factors have been described with apparent opposing roles, such as the highly pro-inflammatory potency of IL-6 and the anti-inflammatory properties of IL-10, thus raising the possibility that STAT3 signaling may fulfill diverse roles in CD4(+) T-cells...
June 20, 2017: European Journal of Immunology
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