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https://www.readbyqxmd.com/read/28088761/amplification-of-unscheduled-dna-synthesis-signal-enables-fluorescence-based-single-cell-quantification-of-transcription-coupled-nucleotide-excision-repair
#1
Franziska Wienholz, Wim Vermeulen, Jurgen A Marteijn
Nucleotide excision repair (NER) comprises two damage recognition pathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER), which remove a wide variety of helix-distorting lesions including UV-induced damage. During NER, a short stretch of single-stranded DNA containing damage is excised and the resulting gap is filled by DNA synthesis in a process called unscheduled DNA synthesis (UDS). UDS is measured by quantifying the incorporation of nucleotide analogues into repair patches to provide a measure of NER activity...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088656/low-dose-aspirin-use-and-survival-in-breast-cancer-patients-a-nationwide-cohort-study
#2
Úna C Mc Menamin, Chris R Cardwell, Carmel M Hughes, Liam J Murray
BACKGROUND: Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. METHODS: We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records...
January 12, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#3
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088572/bcs-class-iv-drugs-highly-notorious-candidates-for-formulation-development
#4
REVIEW
Rohan Ghadi, Neha Dand
BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs...
January 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28088383/evaluating-the-role-of-astrocytes-on-%C3%AE-estradiol-effect-on-seizures-of-pilocarpine-epileptic-model
#5
Masoumeh Sarfi, Mahmoud Elahdadi Salmani, Iran Goudarzi, Taghi Lashkar Boluki, Kataneh Abrari
Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40μg/ µl) was injected subcutaneously from 48 before to 48h after seizure induction...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088107/gaas-laser-therapy-reestablishes-the-morphology-of-the-nmj-and-nachrs-after-injury-due-to-bupivacaine
#6
Cristiane Neves Alessi Pissulin, Paula Aiello Tomé de Souza Castro, Flávio Codina, Carina Guidi Pinto, Ivan Jose Vechetti-Junior, Selma Maria Michelin Matheus
BACKGROUND: Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle...
December 22, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28088016/release-and-cytotoxicity-studies-of-magnetite-ag-antibiotic-nanoparticles-an-interdependent-relationship
#7
Olena Ivashchenko, Anna Woźniak, Emerson Coy, Barbara Peplinska, Jacek Gapinski, Stefan Jurga
Though the cytotoxic properties of magnetite nanoparticles (NPs) are rather well investigated and known to be dose dependent and rather low, surface functionalization can drastically change their properties. To determine whether the cytotoxicity of magnetite/Ag/antibiotic NPs may be associated, among other things, with iron, silver and antibiotic release, this study investigates the release profiles and cytotoxicity of magnetite/Ag/rifampicin and magnetite/Ag/doxycycline NPs compares it similar profiles from magnetite, magnetite/Ag NPs and antibiotics...
January 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28087908/-berberine-regulates-glycemia-via-local-inhibition-of-intestinal-dipeptidyl-peptidase-%C3%A2
#8
Jiesheng Wang, Guanhai Dai, Weijia Li
Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg(-1)·d(-1)), low-dose berberine group (30 mg·kg(-1)·d(-1)), moderate-dose berberine group (60 mg·kg(-1)·d(-1)), and high-dose berberine group (120 mg·kg(-1)·d(-1))...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087907/-effect-of-methyleugenol-on-expression-of-muc5ac-in-nasal-mucosa-of-rats-with-allergic-rhinitis
#9
Nannan Meng, Yun Hou, Yan Gui, Kehu Xi, Youhu Wang, Jing Yang, Hong Chen, Xiaobing Zhang
Objective: To investigate the effect of methyleugenol on expression of MUC5AC in nasal mucosa of rats with allergic rhinitis (AR). Methods: Seventy-two Wistar rats were randomly divided into 6 groups:normal control group, AR group, loratadine group, low-dose methyleugenol group, middle-dose methyleugenol group and high-dose methyleugenol group with 12 rats in each group. AR was induced by intraperitoneal injection of ovalbumin in latter 5 groups. 10 mg loratadine q.d was given to rats in loratadine group by gavage; and 10 mg/kg, 20 mg/kg and 40 mg/kg methyleugenol were given by gavege q...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087906/-effect-and-its-molecular-mechanisms-of-curcumin-on-pulmonary-artery-smooth-muscle-cells-in-rat-model-with-chronic-obstructive-pulmonary-disease
#10
Xiangang Lin, Yenong Chen, Zhuqing Liu
Objective: To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD). Methods: A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087899/increasing-dietary-nitrate-has-no-effect-on-cancellous-bone-loss-or-fecal-microbiome-in-ovariectomized-rats
#11
Melissa N Conley, Cooper Roberts, Thomas J Sharpton, Urszula T Iwaniec, Norman Hord
Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age-related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Six-month-old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham-operated (sham)] were randomized into 3 groups: (1) vehicle (water) control, (2) low-dose nitrate (LDN, 0...
January 13, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28087833/dysregulation-of-map-kinase-signaling-pathways-including-p38mapk-sapk-jnk-and-erk1-2-in-cultured-rat-cerebellar-astrocytes-exposed-to-diphenylarsinic-acid
#12
Takayuki Negishi, Mami Matsumoto, Yayoi Kobayashi, Mikiya Kojima, Fumika Sakaguchi, Kazuaki Takahata, Tomoko Kanehira, Rina Arakaki, Yohei Aoyama, Hikari Yoshida, Rena Yamada, Nobutaka Sumiyoshi, Tomoko Tashiro, Seishiro Hirano, Kenji Yoshida, Kazunori Yukawa
Diphenylarsinic acid (DPAA) was a major compound found in the arsenic poisoning incident that occurred in Kamisu, Ibaraki, Japan in 2003. People exposed to DPAA via contaminated well water suffered from several neurological disorders, including cerebellar symptoms. We previously reported that DPAA induces cellular activation in cultured rat cerebellar astrocytes, dose-dependent promotion of cell growth (low DPAA), cell death (high DPAA), and increased phosphorylation of mitogen-activated protein (MAP) kinases (p38MAPK, SAPK/JNK, and ERK1/2)...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087785/thermolytic-degradation-of-synthetic-cannabinoids-chemical-exposures-and-pharmacological-consequences
#13
Brian F Thomas, Timothy W Lefever, Ricardo A Cortes, Alexander L Kovach, Anderson O Cox, Purvi R Patel, Gerald T Pollard, Julie A Marusich, Richard A Kevin, Thomas F Gamage, Jenny L Wiley
Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "Spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds...
January 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#14
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087456/phase-i-trial-of-total-marrow-and-lymphoid-irradiation-transplant-conditioning-in-patients-with-relapsed-refractory-acute-leukemia
#15
Anthony Stein, Joycelynne Palmer, Ni-Chun Tsai, Monzr M Al Malki, Ibrahim Aldoss, Haris Ali, Ahmed Aribi, Len Farol, Chatchada Karanes, Samer Khaled, An Liu, Margaret O'Donnell, Pablo Parker, Anna Pawlowska, Vinod Pullarkat, Eric Radany, Joseph Rosenthal, Firoozeh Sahebi, Amandeep Salhotra, James F Sanchez, Tim Schultheiss, Ricardo Spielberger, Sandra H Thomas, David Snyder, Ryotaro Nakamura, Guido Marcucci, Stephen J Forman, Jeffrey Wong
Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia (AL) patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28087337/tunicamycin-impairs-olfactory-learning-and-synaptic-plasticity-in-the-olfactory-bulb
#16
Jia Tong, Fumino Okutani, Yoshihiro Murata, Mustuo Taniguchi, Toshiharu Namba, Yu-Jie Wang, Hideto Kaba
Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory...
January 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28087221/varenicline-provokes-impulsive-action-by-stimulating-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-in-the-infralimbic-cortex-in-a-nicotine-exposure-status-dependent-manner
#17
Yu Ohmura, Hitomi Sasamori, Iku Tsutsui-Kimura, Takeshi Izumi, Takayuki Yoshida, Mitsuhiro Yoshioka
Higher impulsivity is a risk factor for criminal involvement and drug addiction. Because nicotine administration enhances impulsivity, the effects of stop-smoking aids stimulating nicotinic acetylcholine receptors (nAChRs) on impulsivity must be determined in different conditions. Our goals were 1) to confirm the relationship between varenicline, a stop-smoking aid and α4β2 nAChR partial agonist, and impulsivity, 2) to elucidate the mechanisms underlying the effects of varenicline, 3) to examine whether a low dose of varenicline that does not evoke impulsive action could block the stimulating effects of nicotine on impulsive action, 4) to determine whether the route of administration could modulate the effects of varenicline on impulsive action, and 5) to determine whether the effects of varenicline on impulsivity could be altered by smoking status...
January 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28086942/external-beam-radiotherapy-for-unresectable-hepatocellular-carcinoma-an-international-multicenter-phase-i-trial-sakk-77-07-and-sasl-26
#18
Evelyn Herrmann, Diana Naehrig, Manfred Sassowsky, Martin Bigler, Jeroen Buijsen, Ilja Ciernik, Daniel Zwahlen, Alessandra Franzetti Pellanda, Andreas Meister, Peter Brauchli, Simona Berardi, Erika Kuettel, Jean-François Dufour, Daniel M Aebersold
PURPOSE: To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC). METHODS: Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if ≥90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54-70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5...
January 13, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28086936/association-between-low-blood-lead-levels-and-increased-risk-of-dental-caries-in-children-a-cross-sectional-study
#19
Young-Suk Kim, Mina Ha, Ho-Jang Kwon, Hae-Young Kim, Youn-Hee Choi
BACKGROUND: The objective of this study was to examine the association between low blood lead levels of <5 μg/dL and the development of dental caries among children. METHODS: The Children's Health and Environment Research (CHEER) group recruited a cohort of 7,059 school-aged children from six Korean cities. The final study populations in the permanent and deciduous teeth groups were 1,564 and 1,241 children, respectively, after excluding 4 children with blood lead levels of >5 μg/dL...
January 13, 2017: BMC Oral Health
https://www.readbyqxmd.com/read/28086886/biochemical-mechanism-underlying-hypertriglyceridemia-and-hepatic-steatosis-hepatomegaly-induced-by-acute-schisandrin-b-treatment-in-mice
#20
Yi Zhang, Jing Zhao, Shu-Feng Zhou, Zhi-Ling Yu, Xiao-Yan Wang, Pei-Li Zhu, Zhu-Sheng Chu, Si-Yuan Pan, Ming Xie, Kam-Ming Ko
BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0...
January 13, 2017: Lipids in Health and Disease
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