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https://www.readbyqxmd.com/read/28228012/investigation-of-thermally-induced-cellular-ablation-and-heat-response-triggered-by-planar-mos2-based-nanocomposite
#1
Shinya Ariyasu, Jing Mu, Xiao Zhang, Ying Huang, Edwin K L Yeow, Hua Zhang, Bengang Xing
In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce the localized heat for targeted ablation of cancer cells. Among various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially-molybdenum disulfide (MoS2) have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability...
February 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28225183/protective-effects-of-araloside-c-against-myocardial-ischaemia-reperfusion-injury-potential-involvement-of-heat-shock-protein-90
#2
Min Wang, Yu Tian, Yu-Yang Du, Gui-Bo Sun, Xu-Dong Xu, Hai Jiang, Hui-Bo Xu, Xiang-Bao Meng, Jing-Yi Zhang, Shi-Lan Ding, Miao-di Zhang, Ming-Hua Yang, Xiao-Bo Sun
The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration-dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca(2+) transients and cell shortening against I/R...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28225027/variable-salinity-responses-of-12-alfalfa-genotypes-and-comparative-expression-analyses-of-salt-response-genes
#3
Devinder Sandhu, Monica V Cornacchione, Jorge F S Ferreira, Donald L Suarez
Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index of the genotypes ranged from 0.39 to 1. The most salt-tolerant genotypes SISA14-1 (G03) and AZ-90ST (G10), the top performers for biomass, exhibited the least effect on shoot number and height. SISA14-1 (G03) accumulated low Na and Cl under salinity...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28221352/dynamic-undocking-and-the-quasi-bound-state-as-tools-for-drug-discovery
#4
Sergio Ruiz-Carmona, Peter Schmidtke, F Javier Luque, Lisa Baker, Natalia Matassova, Ben Davis, Stephen Roughley, James Murray, Rod Hubbard, Xavier Barril
There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein-ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28219205/-preparation-of-chaperone-antigen-peptide-vaccine-derived-from-human-gastric-cancer-stem-cells-and-its-immune-function
#5
Y Q Jiang, Q M Guo, X P Xu, J C Liang, Y Y He, S H An, F Su, C Y Li, C X Huang
Objective: To explore the method of extracting chaperone antigen peptide complexes from gastric cancer stem cells and its immune function. Methods: Gastric cancer stem cells and gastric cancer cells were screened by low temperature ultrasonic lysis. After salting out and dialysis, the lysate supernatant was processed with SDS-PAGE to analyze the expression of chaperone antigen peptide complexes, and then was separated and purified with CNBr-activated SepharoseTM 4B. Reverse high pressure liquid chromatography (HPLC), SDS-PAGE and Western blotting were used to analyze the purity and nature of the acquired albumen...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218749/mechanistic-basis-for-the-recognition-of-a-misfolded-protein-by-the-molecular-chaperone-hsp90
#6
Javier Oroz, Jin Hae Kim, Bliss J Chang, Markus Zweckstetter
The critical toxic species in over 40 human diseases are misfolded proteins. Their interaction with molecular chaperones such as Hsp90, which preferentially interacts with metastable proteins, is essential for the blocking of disease progression. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structure of the misfolded cytotoxic monomer of the amyloidogenic human protein transthyretin, which is characterized by the release of the C-terminal β-strand and perturbations of the A-B loop...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28215707/hsp90-shapes-the-consequences-of-human-genetic-variation
#7
Georgios I Karras, Song Yi, Nidhi Sahni, Máté Fischer, Jenny Xie, Marc Vidal, Alan D D'Andrea, Luke Whitesell, Susan Lindquist
HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function...
February 16, 2017: Cell
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#8
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28212580/network-pharmacology-based-and-clinically-relevant-prediction-of-the-active-ingredients-and-potential-targets-of-chinese-herbs-in-metastatic-breast-cancer-patients
#9
Yu Mao, Jian Hao, Zi-Qi Jin, Yang-Yang Niu, Xue Yang, Dan Liu, Rui Cao, Xiong-Zhi Wu
Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209383/expression-pattern-of-heat-shock-protein-90-in-patients-with-oral-squamous-cell-carcinoma-in-northern-taiwan
#10
W-C Chang, P-T Tsai, C-K Lin, Y-S Shieh, Y-W Chen
Heat shock protein 90 (HSP90), which is expressed in cancer cells, profoundly affects progression, invasion, and metastasis. However, to our knowledge, in East Asia, the correlation between the expression of HSP90 and clinicopathological variables has seldom been discussed. We therefore investigated this and its prognostic value in 36 patients newly diagnosed with oral squamous cell carcinoma (SCC) in northern Taiwan. Samples of tumour and normal samples from the patients were compared immunohistochemically...
February 13, 2017: British Journal of Oral & Maxillofacial Surgery
https://www.readbyqxmd.com/read/28208059/designer-protein-disaggregases-to-counter-neurodegenerative-disease
#11
REVIEW
James Shorter
Protein misfolding and aggregation unify several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. There are no effective therapeutics for these disorders and none that target the reversal of the aberrant protein misfolding and aggregation that cause disease. Here, I showcase important advances to define, engineer, and apply protein disaggregases to mitigate deleterious protein misfolding and counter neurodegeneration. I focus on two exogenous protein disaggregases, Hsp104 from yeast and gene 3 protein from bacteriophages, as well as endogenous human protein disaggregases, including: (a) Hsp110, Hsp70, Hsp40, and small heat-shock proteins; (b) HtrA1; and (c) NMNAT2 and Hsp90...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28207175/design-of-allosteric-stimulators-of-the-hsp90-atpase-as-novel-anticancer-leads
#12
Ilda D'Annessa, Sara Sattin, Jiahui Tao, Marzia Pennati, Carlos Sànchez-Martìn, Elisabetta Moroni, Andrea Rasola, Nadia Zaffaroni, David A Agard, Anna Bernardi, Giorgio Colombo
We rationally designed allosteric compounds that stimulate Hsp90 ATPase activity and show anticancer potencies in the low micromolar to nanomolar range. In parallel, we clarify their mode of action and developed a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities. Our results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics.
February 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28205552/a-class-of-extracellular-vesicles-from-breast-cancer-cells-activates-vegf-receptors-and-tumour-angiogenesis
#13
Qiyu Feng, Chengliang Zhang, David Lum, Joseph E Druso, Bryant Blank, Kristin F Wilson, Alana Welm, Marc A Antonyak, Richard A Cerione
Non-classical secretory vesicles, collectively referred to as extracellular vesicles (EVs), have been implicated in different aspects of cancer cell survival and metastasis. Here, we describe how a specific class of EVs, called microvesicles (MVs), activates VEGF receptors and tumour angiogenesis through a unique 90 kDa form of VEGF (VEGF90K). We show that VEGF90K is generated by the crosslinking of VEGF165, catalysed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28204829/heat-shock-protein-90-akt-pathway-participates-in-the-cardioprotective-effect-of-exogenous-hydrogen-sulfide-against-high-glucose-induced-injury-to-h9c2-cells
#14
Xiao Ke, Jingfu Chen, Longyun Peng, Wei Zhang, Yiying Yang, Xinxue Liao, Liqiu Mo, Ruixian Guo, Jianqiang Feng, Chengheng Hu, Ruqiong Nie
It has been reported that exogenous hydrogen sulfide (H2S) protects against high glucose (HG)-induced cardiac injury and has a modulatory effect on heat shock protein (HSP) and Akt, which play a cardioprotective role. In this study, we examined whether the HSP90/Akt pathway contributes to the protective effects of exogenous H2S against HG-induced injury to H9c2 cardiac cells. Our results revealed that the exposure of H9c2 cardiac cells to 35 mM glucose (HG) for 1 to 24 h decreased the expression of HSP90 and markedly reduced the expression level of phosphorylated (p)-Akt in a time-dependent manner...
February 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#15
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28201527/high-dose-of-antibiotic-colistin-induces-oligomerization-of-molecular-chaperone-hsp90
#16
Shuntaro Togashi, Kyosuke Takahashi, Arisa Tamura, Ikumi Toyota, Shiori Hatakeyama, Atsushi Komatsuda, Ikuru Kudo, Erina Sasaki Kudoh, Tomoya Okamoto, Asami Haga, Asuka Miyamoto, Ewa Grave, Taku Sugawara, Hiroaki Shimizu, Hideaki Itoh
No abstract text is available yet for this article.
February 14, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28199108/application-of-off-rate-screening-in-the-identification-of-novel-pan-isoform-inhibitors-of-pyruvate-dehydrogenase-kinase
#17
Paul A Brough, Lisa Baker, Simon Bedford, Kirsten Brown, Seema Chavda, Victoria Chell, Jalanie D'Alessandro, Nicholas G M Davies, Ben Davis, Loic Le Strat, Alba T Macias, Daniel Maddox, Patrick C Mahon, Andrew J Massey, Natalia Matassova, Sean McKenna, Jonathan D Moore, James B Murray, Christopher J Northfield, Charles Parry, Rachel Parsons, Stephen D Roughley, Terry Shaw, Heather Simmonite, Stephen Stokes, Allan Surgenor, Emma Stefaniak, Alan Robertson, Yikang Wang, Paul Webb, Neil Whitehead, Mike Wood
Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28194559/selenium-deficiency-induced-injury-in-chicken-muscular-stomach-by-downregulating-selenoproteins
#18
Xiaodan Huang, Bin Sun, Jiuli Zhang, Yuhong Gao, Guangxing Li, Ying Chang
The aim of the present study was to examine the effect of selenium (Se) deficiency on the expression of selenoproteins in chicken muscular stomach and to detect the correlation of selenoproteins with muscular stomach injuries. One-day-old broiler chickens were maintained for 55 days on a normal diet (0.2 mg/kg) or a Se-deficient diet (0.033 mg Se/kg). The expression levels of 25 selenoproteins, heat shock proteins (HSPs), and inflammatory factors were then examined by real-time PCR. Following this, the correlation between selenoproteins, HSPs, and inflammatory factors was analyzed by principal component analysis (PCA)...
February 13, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28193840/co-chaperone-hsp70-hsp90-organizing-protein-hop-is-required-for-transposon-silencing-and-pirna-biogenesis
#19
Joseph A Karam, Rasesh Y Parikh, Dhananjaya Nayak, David Rosenkranz, Vamsi K Gangaraju
piRNAs are 26-30nt germ-line specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90 Organizing Protein Homolog (Hop), a co-chaperone, interacts with piRNA binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known if Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ-line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28192191/the-crystal-structure-of-the-hsp90-co-chaperone-cpr7-from-saccharomyces-cerevisiae
#20
Yu Qiu, Qiangqiang Ge, Mingxing Wang, Hui Lv, Mohammad Ebrahimi, Liwen Niu, Maikun Teng, Xu Li
The versatility of Hsp90 can be attributed to the variety of co-chaperone proteins that modulate the role of Hsp90 in many cellular processes. As a co-chaperone of Hsp90, Cpr7 is essential for accelerating the cell growth in an Hsp90-containing trimeric complex. Here, we report the crystal structure of Cpr7 at a resolution of 1.8Å. It consists of an N-terminal PPI domain and a C-terminal TPR domain, and exhibits a U-shape conformation. Our studies revealed the aggregation state of Cpr7 in solution and the interaction properties between Cpr7 and the MEEVD sequence from the C-terminus of Hsp90...
February 9, 2017: Journal of Structural Biology
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