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https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#1
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905362/-characteristics-of-parkinson-s-disease-course-in-the-heterozygous-carriage-of-mutations-in-the-glucocerebrosidase-a-gene
#2
O A Gan'kina, E E Vasenina, O S Levin, E Yu Fedotova, S N Illarioshkin
Parkinson's disease (PD) is a common neurodegenerative disease. Literature sources indicate the association of PD and mutations in the glucocerebrosidase A (GBA) gene. According to our study, the frequency of the two most common mutations in the GBA gene, N370S and L444P, is 1.85%. Mutation carriers have slower progression of motor symptoms, but are more likely to develop drug-induced motor fluctuations and dyskinesia. In carriers of GBA mutations, the severity of cognitive impairment corresponds to age-matched patients without mutations...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#3
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904421/cannabis-induced-moto-cognitive-dysfunction-in-wistar-rats-ameliorative-efficacy-of-nigella-sativa
#4
Aminu Imam, Moyosore Saliu Ajao, Abdulbasit Amin, Wahab Imam Abdulmajeed, Abdulmumin Ibrahim, Olayemi Joseph Olajide, Musa Iyiola Ajibola, Abdulmusawir Alli-Oluwafuyi, Wasiu Gbolahan Balogun
BACKGROUND: Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. METHODS: Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days...
September 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/27904045/puerarin-prevents-lps-induced-osteoclast-formation-and-bone-loss-via-inhibition-of-akt-activation
#5
Yun Zhang, Ming Yan, Qing-Feng Yu, Pei-Fan Yang, Hai-Dong Zhang, Yong-Hong Sun, Zhi-Fen Zhang, Yun-Feng Gao
Osteolysis induced by chronic Gram-negative bacterial infection underlies many bone diseases such as osteomyelitis, septic arthritis, and periodontitis. Drugs that inhibit lipopolysaccharide (LPS)-induced osteolysis are critically needed for the prevention of bone destruction in infective bone diseases. In this study, we assessed the effect of puerarin, a natural isoflavone isolated from Pueraria lobata OHWI root, on LPS-induced osteoclastogenesis and bone loss. Our in vitro study showed that puerarin significantly inhibited LPS-induced osteoclast differentiation from osteoclast precursor RAW264...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903643/effects-of-antihypertensive-agents-on-intestinal-contractility-in-the-spontaneously-hypertensive-rat-angiotensin-receptor-system-down-regulation-by-losartan
#6
Glen S Patten, Mahinda Y Abeywardena
Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus and recently to dysfunction of the gut. The aim of this study was to determine what effect anti-hypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment SHR were treated with enalapril or hydralazine. In the second experiment SHR were treated with losartan with no-treatment as control for both experiments...
November 30, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27903427/anti-inflammatory-effect-of-miltirone-on-inflammatory-bowel-disease-via-tlr4-nf-%C3%AE%C2%BAb-iqgap2-signaling-pathway
#7
Hongjian Wang, Junfei Gu, Xuefeng Hou, Juan Chen, Nan Yang, Ying Liu, Gang Wang, Mei Du, Huihui Qiu, Yi Luo, Ziyu Jiang, Liang Feng
Inflammatory bowel disease (IBD) is characterized by a radical imbalance in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut. This study was conducted to evaluate the anti-inflammation effect of miltirone against IBD in vitro and in vivo, and try to explore the underlying mechanisms. Miltirone could extenuate the loss of colon length and weight caused by TNBS. Additionally, macroscopic scores and DAI were reduced significantly compared with the TNBS group. The levels of TNF-α, IL-1β, IL-6 and IL-8 were increased significantly with the induction by TNBS (100mg/kg) or LPS (0...
November 27, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27903226/protective-effects-of-caffeic-acid-and-the-alzheimer-s-brain-an-update
#8
Solomon Habtemariam
Caffeic acid (CA) and related phenylpropanoic acids are ubiquitous natural products of the shikimic acid pathway origin. Due to the presence of diorthohydroxyl aromatic (catecholic) moiety, CA is not only one of the most potent antioxidant phenyl propanoids but also display numerous other pharmacological effects ranging from antiinflammatory to anticancer effects. Recent studies also demonstrated that CA both in its free form or conjugated with other groups such as quinic acid and sugars display profound effects in the brain including protection from toxicity induced by a variety of agents and/or experimental models of Alzheimer's disease (AD)...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27902980/gene-expression-profiling-and-functional-characterization-of-macrophages-in-response-to-circulatory-microparticles-produced-during-trypanosoma-cruzi-infection-and-chagas-disease
#9
Imran H Chowdhury, Sue-Jie Koo, Shivali Gupta, Lisa Yi Liang, Bojlul Bahar, Laura Silla, Julio Nuñez-Burgos, Natalia Barrientos, Maria Paola Zago, Nisha Jain Garg
BACKGROUND: Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHODS: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs...
December 1, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27902963/homology-modeling-and-molecular-dynamics-simulation-of-the-hif2%C3%AE-degradation-related-hif2%C3%AE-vhl-complex
#10
Xiaotian Dong, Xiaoru Su, Jiong Yu, Jingqi Liu, Xiaowei Shi, Qiaoling Pan, Jinfeng Yang, Jiajia Chen, Lanjuan Li, Hongcui Cao
BACKGROUND: Hypoxia-inducible factor 2 alpha (HIF2α), prolyl hydroxylase domain protein 2 (PHD2), and the von Hippel Lindau tumor suppressor protein (pVHL) are three principal proteins in the oxygen-sensing pathway. Under normoxic conditions, a conserved proline in HIF2α is hydroxylated by PHD2 in an oxygen-dependent manner, and then pVHL binds and promotes the degradation of HIF2α. However, the crystal structure of the HIF2α-pVHL complex has not yet been established, and this has limited research on the interaction between HIF and pVHL...
November 21, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#11
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902448/rasgrp1-promotes-amphetamine-induced-motor-behavior-through-a-rhes-interaction-network-rhesactome-in-the-striatum
#12
Neelam Shahani, Supriya Swarnkar, Vincenzo Giovinazzo, Jenny Morgenweck, Laura M Bohn, Catherina Scharager-Tapia, Bruce Pascal, Pablo Martinez-Acedo, Kshitij Khare, Srinivasa Subramaniam
The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and attention-deficit/hyperactivity disorder (ADHD), trigger dopamine release in the striatum. The guanosine triphosphatase Ras homolog enriched in the striatum (Rhes) inhibits dopaminergic signaling in the striatum, is implicated in HD and L-dopa-induced dyskinesia, and has a role in striatal motor control...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27901208/gastric-and-renal-effects-of-cox-2-selective-and-non-selective-nsaids-in-rats-receiving-low-dose-aspirin-therapy
#13
Marcella Goetz Moro, Paula Katherine Vargas Sanchez, Mayara Vitorino Gevert, Emeline Maria Baller, Ana Flávia Tostes, Ana Caroline Lupepsa, Sinvaldo Baglie, Gilson Cesar Nobre Franco
The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy...
November 28, 2016: Brazilian Oral Research
https://www.readbyqxmd.com/read/27900874/human-pluripotent-stem-cells-in-modeling-human-disorders-the-case-of-fragile-x-syndrome
#14
Dan Vershkov, Nissim Benvenisty
Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS...
November 30, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27899918/mechanistic-basis-of-antimicrobial-actions-of-silver-nanoparticles
#15
REVIEW
Tikam Chand Dakal, Anu Kumar, Rita S Majumdar, Vinod Yadav
Multidrug resistance of the pathogenic microorganisms to the antimicrobial drugs has become a major impediment toward successful diagnosis and management of infectious diseases. Recent advancements in nanotechnology-based medicines have opened new horizons for combating multidrug resistance in microorganisms. In particular, the use of silver nanoparticles (AgNPs) as a potent antibacterial agent has received much attention. The most critical physico-chemical parameters that affect the antimicrobial potential of AgNPs include size, shape, surface charge, concentration and colloidal state...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#16
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#17
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27899257/juglanin-induces-apoptosis-and-autophagy-in-human-breast-cancer-progression-via-ros-jnk-promotion
#18
Zhu-Lei Sun, Jin-Long Dong, Jiang Wu
Breast cancer is one of the most common primary malignant tumors of among women, the long-term survival of which has stagnated in the past decades. Juglanin as a natural production mainly extracted from green walnut husks of Juglans mandshurica has been defined as the functional composition among a series of compounds. It showed powerful protective effect in various diseases by inhibiting inflammation and tumor cells growth. However, the effect of juglanin on human breast cancer and the underlying mechanisms remains to be elucidated...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27896850/zebrafish-larva-as-a-reliable-model-for-in-vivo-assessment-of-membrane-remodeling-involvement-in-the-hepatotoxicity-of-chemical-agents
#19
Normand Podechard, Martine Chevanne, Morgane Fernier, Arnaud Tête, Aurore Collin, Doris Cassio, Olivier Kah, Dominique Lagadic-Gossmann, Odile Sergent
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896297/a-mouse-model-of-multi-drug-resistant-staphylococcus-aureus-induced-ocular-disease
#20
Nicole M Broekema, Inna V Larsen, Erika S Naruzawa, Marcin Filutowicz, Aaron W Kolb, Leandro B C Teixeira, Curtis R Brandt
Staphylococcus aureus infection of the cornea is a significant threat to vision. The percentage of bacterial isolates resistant to antibiotics is increasing as is the percentage of infections caused by methicillin resistant isolates. There is a critical need for additional therapeutic approaches and their development will require the use of animal models to test efficacy. Two mouse models of S. aureus keratitis have been described but only quantified stromal keratitis (corneal clouding and perforation). We have extended these models using the methicillin resistant S...
November 2016: Journal of Ocular Biology
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