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https://www.readbyqxmd.com/read/28813000/an-ameliorated-prediction-of-drug-target-interactions-based-on-multi-scale-discrete-wavelet-transform-and-network-features
#1
Cong Shen, Yijie Ding, Jijun Tang, Xinying Xu, Fei Guo
The prediction of drug-target interactions (DTIs) via computational technology plays a crucial role in reducing the experimental cost. A variety of state-of-the-art methods have been proposed to improve the accuracy of DTI predictions. In this paper, we propose a kind of drug-target interactions predictor adopting multi-scale discrete wavelet transform and network features (named as DAWN) in order to solve the DTIs prediction problem. We encode the drug molecule by a substructure fingerprint with a dictionary of substructure patterns...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812983/a-microfluidic-platform-for-modeling-metastatic-cancer-cell-matrix-invasion
#2
Laura Blaha, Chentian Zhang, Mario Cabodi, Joyce Y Wong
Invasion of the extracellular matrix is a critical step in the colonization of metastatic tumors. The invasion process is thought to be driven by both chemokine signaling and interactions between invading cancer cells and physical components of the metastatic niche, including endothelial cells that line capillary walls and serve as a barrier to both diffusion and invasion of the underlying tissue. Transwell chambers, a tool for generating artificial chemokine gradients to induce cell migration, have facilitated recent work to investigate the chemokine contributions to matrix invasion...
August 16, 2017: Biofabrication
https://www.readbyqxmd.com/read/28812944/binding-forces-between-a-novel-schiff-base-palladium-ii-complex-and-two-carrier-proteins-human-serum-albumi-and%C3%AE-lactoglobulin
#3
Somaye Shahraki, Ali Heydari
Ligand binding studies on carrier proteins are crucial in determining the pharmacological properties of drug candidates. Here, a new palladium(II) complex was synthesized and characterized. The in vitro binding studies of this complexwith two carrier proteins, human serum albumin (HSA) and β-lactoglobulin (βLG) was investigated by employing biophysical techniques as well as computational modeling. The experimental results showed thatthe Pd(II) complex interacted with two carrier proteins with moderate binding affinity (Kb ~̴ 0...
August 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28812431/oral-administration-of-curcumin-attenuates-visceral-hyperalgesia-through-inhibiting-phosphorylation-of-trpv1-in-rat-model-of-ulcerative-colitis
#4
Mei Yang, Juan Wang, Chunxue Yang, Hongxiu Han, Weifang Rong, Guohua Zhang
Background Curcumin has been reported to have anti-inflammatory and anti-nociceptive effects. The present study was designed to explore the potential therapeutic effects of curcumin on visceral hyperalgesia and inflammation in a rat model of ulcerative colitis. We observed the effects of orally administered curcumin on the disease activity index, histological change in colon, colorectal distension-induced abdominal withdrawal reflex, the expression of transient receptor potential vanilloid 1 (TRPV1) and phosphorylated TRPV1 in dextran sulfate sodium-induced colitis rats...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28812356/single-molecule-nanopore-spectrometry-for-peptide-detection
#5
Amy E Chavis, Kyle T Brady, Grace A Hatmaker, Christopher E Angevine, Nuwan Kothalawala, Amala Dass, Joseph W F Robertson, Joseph E Reiner
Sensing and characterization of water-soluble peptides is of critical importance in a wide variety of bioapplications. Single molecule nanopore spectrometry (SMNS) is based on the idea that one can use biological protein nanopores to resolve different sized molecules down to limits set by the blockade duration and noise. Previous work has shown that this enables discrimination between polyethylene glycol (PEG) molecules that differ by a single monomer unit. This paper describes efforts to extend SMNS to a variety of biologically relevant, water-soluble peptides...
August 16, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28812259/evolutionary-dynamics-in-the-fungal-polarization-network-a-mechanistic-perspective
#6
REVIEW
Eveline T Diepeveen, Leila Iñigo de la Cruz, Liedewij Laan
Polarity establishment underlies proper cell cycle completion across virtually all organisms. Much progress has been made in generating an understanding of the structural and functional components of this process, especially in model species. Here we focus on the evolutionary dynamics of the fungal polarization protein network in order to determine general components and mechanistic principles, species- or lineage-specific adaptations and the evolvability of the network. The currently available genomic and proteomic screens in a variety of fungal species have shown three main characteristics: (1) certain proteins, processes and functions are conserved throughout the fungal clade; (2) orthologous functions can never be assumed, as various cases have been observed of homologous loci with dissimilar functions; (3) species have, typically, various species- or lineage-specific proteins incorporated in their polarization network...
August 15, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28812215/proteomic-alterations-associated-with-biomechanical-dysfunction-are-early-processes-in-the-emilin1-deficient-mouse-model-of-aortic-valve-disease
#7
P M Angel, D A Narmoneva, M K Sewell-Loftin, C Munjal, L Dupuis, B J Landis, A Jegga, C B Kern, W D Merryman, H S Baldwin, G M Bressan, Robert B Hinton
Aortic valve (AV) disease involves stiffening of the AV cusp with progression characterized by inflammation, fibrosis, and calcification. Here, we examine the relationship between biomechanical valve function and proteomic changes before and after the development of AV pathology in the Emilin1-/- mouse model of latent AV disease. Biomechanical studies were performed to quantify tissue stiffness at the macro (micropipette) and micro (atomic force microscopy (AFM)) levels. Micropipette studies showed that the Emilin1-/- AV annulus and cusp regions demonstrated increased stiffness only after the onset of AV disease...
August 15, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28812176/effects-of-sodium-houttuyfonate-on-pulmonary-inflammation-in-copd-model-rats
#8
Zhonghua Wu, Bo Tan, Haiying Zhang, Yinuo Guo, Yanjie Tu, Furong Qiu, Aidong Yang
The anti-inflammatory effect of sodium houttuyfonate (SH), an herbal-originated drug that used in China clinically, was investigated on chronic obstructive pulmonary disease (COPD) inflammatory model rats induced by combination usage of cigarette smoke (CS) and lipopolysaccharide (LPS). The morphology of the lung tissue, the expression levels of cytokines in the bronchoalveolar lavage fluid (BALF), the protein levels of TLR4, NF-κB p65, and SIGIRR, and the mRNA levels of TLR4, MyD88, NF-κB p65, and SIGIRR in lung tissues were investigated, respectively...
August 15, 2017: Inflammation
https://www.readbyqxmd.com/read/28812173/melatonin-attenuates-pain-hypersensitivity-and-decreases-astrocyte-mediated-spinal-neuroinflammation-in-a-rat-model-of-oxaliplatin-induced-pain
#9
Ye-Song Wang, Yuan-Yuan Li, Wei Cui, Li-Bin Li, Zhao-Cai Zhang, Bao-Ping Tian, Gen-Sheng Zhang
Neuroinflammatory response in spinal dorsal horn has been demonstrated to be a critical factor in oxaliplatin-induced pain. Melatonin has been shown to have anti-inflammatory and anti-allodynia effects in both preclinical and clinical studies. In the present study, we investigated the role of systemic administration of melatonin on oxaliplatin-induced pain. Intraperitoneal (i.p.) injection with oxaliplatin induced significantly mechanical allodynia and thermal hyperalgesia. Melatonin (i.p.) significantly alleviated mechanical allodynia and thermal hyperalgesia in the oxaliplatin but not sham-treated rats...
August 15, 2017: Inflammation
https://www.readbyqxmd.com/read/28812062/clinical-and-experimental-studies-of-a-novel-p525r-fus-mutation-in-amyotrophic-lateral-sclerosis
#10
Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St Clair, Edward J Kasarskis, Haining Zhu
OBJECTIVE: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models. METHODS: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28812050/caveats-in-the-established-understanding-of-cmt1a
#11
Jun Li
Charcot-Marie-Tooth disease type-1A (CMT1A) is one of the most common types of inherited peripheral nerve diseases. It is caused by the trisomy of chromosome 17p12 (c17p12), a large DNA segment of 1.4 Mb containing PMP22 plus eight other genes. The size of c17p12 is formidable for any cloning technique to manipulate, and thus precludes production of models in vitro and in vivo that can precisely recapitulate the genetic alterations in humans with CMT1A. This limitation and other factors have led to several assumptions, which have yet been carefully scrutinized, serving as key principles in our understanding of the disease...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28812049/importance-of-adiponectin-activity-in-the-pathogenesis-of-alzheimer-s-disease
#12
REVIEW
Masaaki Waragai, Gilbert Ho, Yoshiki Takamatsu, Kazunari Sekiyama, Shuei Sugama, Takato Takenouchi, Eliezer Masliah, Makoto Hashimoto
A recent study suggested that insulin resistance may play a central role in the pathogenesis of Alzheimer's disease (AD). In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD. These results are unanticipated because AD has been linked to type II diabetes and other metabolic disorders in which hypoadiponectinemia has been firmly established, and because APN ameliorated neuropathological features in a mouse model of neurodegeneration...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28812047/selected-missense-mutations-impair-frataxin-processing-in-friedreich-ataxia
#13
Elisia Clark, Jill S Butler, Charles J Isaacs, Marek Napierala, David R Lynch
OBJECTIVE: Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. METHODS: Immunocytochemical studies and subcellular fractionation were performed to study FXN import into the mitochondria and examine the mechanism by which mutations impair FXN processing...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#14
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#15
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811894/the-conceptual-advances-of-carcinogenic-sequence-model-in-high-grade-serous-ovarian-cancer
#16
Hiroshi Kobayashi, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada, Kenji Ogawa, Naoki Kawahara
The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC)...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28811869/pro-and-antioxidant-functions-of-the-peroxisome-mitochondria-connection-and-its-impact-on-aging-and-disease
#17
REVIEW
Amparo Pascual-Ahuir, Sara Manzanares-Estreder, Markus Proft
Peroxisomes and mitochondria are the main intracellular sources for reactive oxygen species. At the same time, both organelles are critical for the maintenance of a healthy redox balance in the cell. Consequently, failure in the function of both organelles is causally linked to oxidative stress and accelerated aging. However, it has become clear that peroxisomes and mitochondria are much more intimately connected both physiologically and structurally. Both organelles share common fission components to dynamically respond to environmental cues, and the autophagic turnover of both peroxisomes and mitochondria is decisive for cellular homeostasis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#18
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28811823/protective-barrier-properties-of-rhinosectan-%C3%A2-spray-containing-xyloglucan-on-an-organotypic-3d-airway-tissue-model-mucilair-results-of-an-in-vitro-study
#19
Barbara De Servi, Francesco Ranzini, Núria Piqué
BACKGROUND: To evaluate barrier protective properties of Rhinosectan(®) spray, a medical device containing xyloglucan, on nasal epithelial cells (MucilAir). METHODS: MucilAir-Nasal, a three-dimensional organotypic (with different cell types) airway tissue model, was treated with the medical device Rhinosectan(®) (30 µL) or with controls (Rhinocort-budesonide-or saline solution). The protective barrier effects of Rhinosectan(®) were evaluated by: TEER (trans-epithelial electrical resistance) (preservation of tight junctions), Lucifer Yellow assay (preservation of paracellular flux) and confocal immunofluorescence microscopy (localization of tight junction proteins)...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28811710/single-amino-acid-mutation-of-sr-bi-decreases-infectivity-of-hepatitis-c-virus-derived-from-cell-culture-in-a-cell-culture-model
#20
Rong Gao, Wei Gao, Gang Xu, Jie Xu, Hao Ren
AIM: To investigate the effect of a single amino acid mutation in human class B scavenger receptor I (SR-BI) on the infectivity of cell culture-derived hepatitis C virus (HCVcc) in SR-BI knock-down Huh7-siSR-BI cells. METHODS: Site-directed mutagenesis was used to construct the SR-BI S112F mutation, and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-siSR-BI cells were transfected with SR-BI S112F, SR-BI wild type (WT) and control plasmids, and then infected with HCVpp (HCV pseudoparticles) and hepatitis C virus derived from cell culture (HCVcc)...
July 28, 2017: World Journal of Gastroenterology: WJG
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