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https://www.readbyqxmd.com/read/28101166/hsp70-inducer-17-allylamino-demethoxygeldanamycin-provides-neuroprotection-via-anti-inflammatory-effects-in-a-rat-model-of-traumatic-brain-injury
#1
Youquan Gu, Jun Chen, Tianhong Wang, Chaoning Zhou, Zhaodong Liu, Lanhua Ma
Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are important pro-inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17-allylamino-demethoxygeldanamycin (17-AAG), to evaluate its potential as a treatment for patients with TBI...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28092423/-1-h-qnmr-quantification-of-annonaceous-acetogenins-in-crude-extracts-of-annona-muricata-l-fruit-pulp
#2
Natacha Bonneau, Timothé Cynober, Jean-Christophe Jullian, Pierre Champy
INTRODUCTION: Annonaceous acetogenins (AAGs) constitute a group of environmental neurotoxins, possibly implicated in sporadic atypical Parkinsonism/dementia complexes. The recent evidencing of complex mixtures of AAGs in edible fruits and derived food products requires efficient and practical analytical tools for an estimation of human exposure. OBJECTIVE: To develop a simple method for the direct quantitation of the majority of AAGs (sub-types 1a and 1b) within crude extracts, using commonly available (1) H-NMR spectrometers, for food control...
January 16, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28091979/blood-perfusion-in-osteomyelitis-studied-with-15-o-water-pet-in-a-juvenile-porcine-model
#3
Lars Jødal, Ole L Nielsen, Pia Afzelius, Aage K O Alstrup, Søren B Hansen
BACKGROUND: Osteomyelitis is a serious disease which can be difficult to treat despite properly instituted antibiotic therapy. This appears to be related at least partly to degraded vascularisation in the osteomyelitic (OM) lesions. Studies of perfusion in OM bones are, however, few and not quantitative. Quantitative assessment of perfusion could aid in the selection of therapy. A non-invasive, quantitative way to study perfusion is dynamic [(15)O]water positron emission tomography (PET)...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28067803/regulation-of-viral-replication-apoptosis-and-pro-inflammatory-responses-by-17-aag-during-chikungunya-virus-infection-in-macrophages
#4
Tapas K Nayak, Prabhudutta Mamidi, Abhishek Kumar, Laishram Pradeep K Singh, Subhransu S Sahoo, Soma Chattopadhyay, Subhasis Chattopadhyay
Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively...
January 6, 2017: Viruses
https://www.readbyqxmd.com/read/28062368/epothilone-b-based-3-in-1-polymeric-micelle-for-anticancer-drug-therapy
#5
Dae Hwan Shin, Glen S Kwon
Epothilones are microtubule inhibitors that are promising alternatives to paclitaxel due to enhanced anticancer efficacy. While epothilones are slightly more water soluble than paclitaxel and more active against paclitaxel-resistant cells, they still require formulation with Cremophor EL and/or cosolvents and drug resistance still limits therapeutic efficacy. In this report, we showed that the combinational treatment of epothilone B (EpoB), 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, Hsp90 inhibitor), and rapamycin (mTOR inhibitor) displays strong anticancer activity in vitro and in vivo...
January 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28053100/heat-shock-protein-90-ensures-efficient-mumps-virus-replication-by-assisting-with-viral-polymerase-complex-formation
#6
Hiroshi Katoh, Toru Kubota, Yuichiro Nakatsu, Maino Tahara, Minoru Kidokoro, Makoto Takeda
: Paramyxoviral RNAs are synthesized by a viral RNA-dependent RNA polymerase (RdRp) consisting of the large (L) protein and its cofactor phosphoprotein (P protein). The L protein is a multifunctional protein that catalyzes RNA synthesis, mRNA capping and mRNA polyadenylation. Growing evidence shows that the stability of several paramyxovirus L proteins is regulated by heat shock protein 90 (Hsp90). In this study, we demonstrated that Hsp90 activity was important for mumps virus (MuV) replication...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signaling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#7
Feng Zhang, Meng Hao, Huanhuan Jin, Zhen Yao, Naqi Lian, Li Wu, Jiangjuan Shao, Anping Chen, Shizhong Zheng
BACKGROUND AND PURPOSE: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signaling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were intoxicated with carbon tetrachloride for in vivo evaluation of hepatic angiogenesis and fibrotic injury. Diversified molecular approaches including real-time PCR, Western blot, luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay, and co-immunoprecipitation were used to investigate the underlying mechanisms in vitro...
January 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28036294/hsp90-n-and-c-terminal-double-inhibition-synergistically-suppresses-bcr-abl-positive-human-leukemia-cells
#8
Chun Chen, Yingting Zhuang, Xianling Chen, Xiaole Chen, Ding Li, Yingjuan Fan, Jianhua Xu, Yuanzhong Chen, Lixian Wu
Heat shock protein 90 (Hsp90) contains amino (N)-terminal domain, carboxyl(C)-terminal domain, and middle domains, which activate Hsp90 chaperone function cooperatively in tumor cells. One terminal occupancy might influence another terminal binding with inhibitor. The Bcr-Abl kinase is one of the Hsp90 clients implicated in the pathogenesis of chronic myeloid leukemia (CML). Present studies demonstrate that double inhibition of the N- and C-terminal termini can disrupt Hsp90 chaperone function synergistically, but not antagonistically, in Bcr-Abl-positive human leukemia cells...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032595/prospective-identification-of-resistance-mechanisms-to-hsp90-inhibition-in-kras-mutant-cancer-cells
#9
Arefeh Rouhi, Christina Miller, Sarah Grasedieck, Stefanie Reinhart, Britta Stolze, Hartmut Döhner, Florian Kuchenbauer, Lars Bullinger, Stefan Fröhling, Claudia Scholl
Inhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012306/interaction-of-anticancer-drug-clofarabine-with-human-serum-albumin-and-human-%C3%AE-1-acid-glycoprotein-spectroscopic-and-molecular-docking-approach
#10
Mohammad Rehan Ajmal, Saima Nusrat, Parvez Alam, Nida Zaidi, Mohsin Vahid Khan, Masihuz Zaman, Yasser E Shahein, Mohamed H Mahmoud, Gamal Badr, Rizwan Hasan Khan
The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins found abundantly in human plasma, Human Serum Albumin (HSA) and α-1 acid glycoprotein (AAG) was investigated by spectroscopic and molecular modeling methods. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of HSA and AAG is quenched by clofarabine and the static mode of fluorescence quenching is operative. UV-vis spectroscopy deciphered the formation of ground state complex between anticancer drug and the two studied proteins...
December 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28009484/hsp90-inhibition-suppresses-inflammatory-response-and-reduces-carotid-atherosclerotic-plaque-formation-in-apoe-mice
#11
Hongmei Mu, Liyong Wang, Lei Zhao
AIM: Emerging evidences indicate that heat shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In the present study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature. METHODS: HSP90-overexpression lentivirus (Lenti-HSP90) was used to transfect apoE(-/-) mice after constrictive collars were planted at the right common carotid arteries. RESULTS: As a result, HSP90 gene overexpression led to reduction in en face plaque area, and increase in unstable plaque with heavier accumulation of lipids...
December 23, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27996306/mapping-qtls-associated-with-agronomic-and-physiological-traits-under-terminal-drought-and-heat-stress-conditions-in-wheat-triticum-aestivum-l
#12
Sirous Tahmasebi, Bahram Heidari, Hassan Pakniyat, C Lynne McIntyre
Wheat crops frequently experience a combination of abiotic stresses in the field, but most quantitative trait loci (QTL) studies have focused on the identification of QTLs for traits under single stress field conditions. A recombinant inbred line (RIL) population derived from SeriM82 × Babax was used to map QTLs under well-irrigated, heat, drought, and a combination of heat and drought stress conditions in two years. A total of 477 DNA markers were used to construct linkage groups that covered 1619.6 cM of the genome, with an average distance of 3...
January 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/27974920/oxidative-stress-in-androgenetic-alopecia
#13
REVIEW
B E Prie, L Iosif, I Tivig, I Stoian, C Giurcaneanu
: Rationale:Androgenetic alopecia is not considered a life threatening disease but can have serious impacts on the patient's psychosocial life. Genetic, hormonal, and environmental factors are considered responsible for the presence of androgenetic alopecia. Recent literature reports have proved the presence of inflammation and also of oxidative stress at the level of dermal papilla cells of patients with androgenetic alopecia Objective:We have considered of interest to measure the oxidative stress parameters in the blood of patients with androgenetic alopecia Methods and results:27 patients with androgenetic alopecia and 25 age-matched controls were enrolled in the study...
January 2016: Journal of Medicine and Life
https://www.readbyqxmd.com/read/27894402/hsp90-inhibitor-enhances-anti-proliferative-and-apoptotic-effects-of-celecoxib-on-ht-29-colorectal-cancer-cells-via-increasing-bax-bcl-2-ratio
#14
A Mohammadi, M M Yaghoobi, A GholamhoseynianNajar, B Kalantari-Khandani, H Sharifi, M Saravani
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#15
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27867076/the-dna-chaperone-hmgb1-potentiates-the-transcriptional-activity-of-rel1a-in-the-mosquito-aedes-aegypti
#16
Anderson de Mendonça Amarante, Natapong Jupatanakul, Isabel Caetano de Abreu da Silva, Vitor Coutinho Carneiro, Amanda Roberta Revoredo Vicentino, George Dimopolous, Octávio Augusto C Talyuli, Marcelo Rosado Fantappié
High Mobility Group protein 1 (HMGB1) is a non-histone, chromatin-associated nuclear protein that functions in regulating eukaryotic gene expression. We investigated the influence and mechanism of action of Aedes aegypti HMGB1 (AaHMGB1) on mosquito Rel1A-mediated transcription from target gene promoters. The DNA-binding domain (RHD) of AaRel1A was bacterially expressed and purified, and AaHMGB1 dramatically enhanced RHD binding to consensus NF-kB/Rel DNA response elements. Luciferase reporter analyses using a cecropin gene promoter showed that AaHMGB1 potentiates the transcriptional activity of AaRel1A in Aag-2 cells...
January 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27862436/redefining-the-phenotype-of-heat-shock-protein-90-hsp90-inhibitors
#17
Yao Wang, Yen Chin Koay, Shelli Renee McAlpine
Comparing the phenotypes produced when cells are treated with the Hsp90 inhibitors AUY922 or 17-AAG (classical inhibitors) to cells with Hsp90alpha knocked down reveals that the knockdown phenotype is unique from that produced by the inhibitors. Pull-down assays using classical inhibitors verify that these molecules do not bind to Hsp90 as their primary target. Classical inhibitors induce similar protein markers as other anti-cancer therapies Cisplatin and bortezomib, suggesting that AUY922 and 17-AAG act on targets other than Hsp90 and kill cells through multiple mechanisms...
November 8, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27829290/hsp90-inhibitors-in-the-context-of-heat-shock-and-the-unfolded-protein-response-effects-on-a-primary-canine-pulmonary-adenocarcinoma-cell-line
#18
Arin N Graner, Justin E Hellwinkel, Alex M Lencioni, Helen J Madsen, Tessa A Harland, Paul Marchando, Ger J Nguyen, Mary Wang, Laura M Russell, Lynne T Bemis, Thomas J Anchordoquy, Michael W Graner
BACKGROUND: Agents targeting HSP90 and GRP94 are seldom tested in stressed contexts such as heat shock (HS) or the unfolded protein response (UPR). Tumor stress often activates HSPs and the UPR as pro-survival mechanisms. This begs the question of stress effects on chemotherapeutic efficacy, particularly with drugs targeting chaperones such as HSP90 or GRP94. We tested the utility of several HSP90 inhibitors, including PU-H71 (targeting GRP94), on a primary canine lung cancer line under HS/UPR stress compared to control conditions...
December 20, 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27821014/novel-mutation-of-the-translation-initiation-codon-of-the-%C3%AE-1-globin-gene-atg-aag-or-hba1-c-2t-a
#19
John S Waye, Barry Eng, Meredith Hanna, Betty-Ann Hohenadel, Lisa Nakamura, Lynda Walker
We report two Italian-Canadian families with α(+)-thalassemia (α(+)-thal) trait caused by a novel mutation of the translation initiation codon of the α1-globin gene (ATG>AAG or HBA1:c.2T>A). This is the tenth reported α-thal mutation involving the translation initiation codon or the conserved Kozak consensus sequences of the HBA2 or HBA1 genes.
September 2016: Hemoglobin
https://www.readbyqxmd.com/read/27799473/ef-g-catalyzed-translocation-dynamics-in-the-presence-of-ribosomal-frameshifting-stimulatory-signals
#20
Hee-Kyung Kim, Ignacio Tinoco
Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA. Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin...
October 30, 2016: Nucleic Acids Research
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