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https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#1
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29778048/pathogens-constancy-harbinger-of-nosocomial-infection-cum-identification-of-resistant-genes-and-drug-designing
#2
Sana Farooq Ahmad, Ibrar Khan, Abdul Wadood, Sadiq Azam, Noor Rehman, Muhammad Waqas, Kashif Bashir, Asaf Ali Khan
Hospitals are the most prominent places for the growth and spread of bacteria which are resistant to the available antibiotics. This antibiotic resistance is due to the over and misuse of antibiotic dosages of a high-density of patient population which are in frequent interaction with inanimate items of the hospitals and the consequent risk of cross infection. Out of 1010 samples of the current study, 510 (50.49%) were culture positive of which 329 (64.5%) were Gram-positive while 181 (35.49%) Gram negative...
April 22, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29778014/expression-of-grape-acs1-in-tomato-decreases-ethylene-and-alters-the-balance-between-auxin-and-ethylene-during-shoot-and-root-formation
#3
Xia Ye, Mengmeng Fu, Yu Liu, Dongliang An, Xianbo Zheng, Bin Tan, Jidong Li, Jun Cheng, Wei Wang, Jiancan Feng
Ethylene plays an important role in the grape rachis, where its production can be 10 times higher than in the berry. VvACS1 is the only rachis-specific ACC synthase (ACS) gene, and its expression is coincident with ethylene production in the rachis of Vitis vinifera 'Thompson seedless'. VvACS1 was cloned and ectopically expressed in tomato (Solanum lycopersicum 'Moneymaker'). Lateral buds were increased in two- or four-week-old 35s∷VvACS1 transgenic tomato plants after transplanting. Compared with wild-type (WT) plants, the transgenic tomato plants showed higher expression of the VvACS1 gene in the flowers, leaves, rachis, and fruits...
May 4, 2018: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#4
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777991/co-evolutionary-associations-between-root-associated-microbiomes-and-root-transcriptomes-in-wild-and-cultivated-rice-varieties
#5
Lei Tian, Shaohua Shi, Lina Ma, Fahad Nasir, Xiujun Li, Lam-Son Phan Tran, Chunjie Tian
The plants and root-associated microbiomes are closely related. Plant metabolic substances can serve as a nutrient source for the microbiome, and in return, the microbiome can regulate the production of plant metabolic substances. Wild rice (Oryza rufipogon), as the ancestor of cultivated rice (Oryza sativa), has changed several metabolic pathways and root-associated microbiome during evolution. Thus, the study of the different associations between metabolic pathways and root-associated microbiomes in wild and cultivated rice varieties is important for rice breeding...
April 13, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29777988/insight-into-structural-requirements-for-selective-and-or-dual-cxcr3-and-cxcr4-allosteric-modulators
#6
Anja Kolarič, Urban Švajger, Tihomir Tomašič, Regine Brox, Theresa Frank, Nikola Minovski, Nuska Tschammer, Marko Anderluh
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation...
May 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29777985/liquid-chromatography-tandem-mass-spectrometry-for-the-quantification-of-moxifloxacin-ciprofloxacin-daptomycin-caspofungin-and-isavuconazole-in-human-plasma
#7
Julian Hösl, André Gessner, Nahed El-Najjar
A simple and precise ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous analysis of five anti-infective agents used to treat severe infections [three antibiotics (daptomycin, moxifloxacin, ciprofloxacin) and two antifungals (isavuconazole, caspofungin)] in human plasma. Sample preparation was based on protein precipitation with ice cold methanol. All five agents were analyzed with the corresponding isotopically labeled internal standards. All analytes were detected in multiple reactions monitoring (MRM) using API 4000 triple-quadrupole mass spectrometer with electrospray (ESI) source operating in positive mode...
May 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29777961/non-viral-delivery-of-an-optogenetic-tool-into-cells-with-self-healing-hydrogel
#8
Fu-Yu Hsieh, Hao-Wei Han, Xiao-Ru Chen, Chii-Shen Yang, Yen Wei, Shan-Hui Hsu
Optogenetics offers unique, temporally precise control of neural activity in genetically targeted specific neurons that express light-sensitive opsin molecules. Three-dimensional (3D) delivery of optogenetics can be realized by co-injection of bacteriorhodopsin (HEBR) plasmid with a chitosan-based self-healing hydrogel with strong shear-thinning properties. The HEBR protein shows photoelectrical properties and can be used as an optical switch for cell activation. We optimize the shear force generated during the process of injection (∼100 Pa), which is transient because of the self-healing nature of the hydrogel...
May 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29777941/characterization-of-the-binding-of-a-novel-antitumor-drug-ibrutinib-with-human-serum-albumin-insights-from-spectroscopic-calorimetric-and-docking-studies
#9
Bin Tang, Peixiao Tang, Jiawei He, Hongqin Yang, Hui Li
Ibrutinib (IBR) is a novel Bruton's tyrosine kinase inhibitor and shows good efficacy for several B-cell malignancies. In the current study, the molecular mechanism of the interaction between IBR and the transport protein human serum albumin (HSA) was ascertained by spectroscopic, calorimetric, and docking studies. Detailed investigations on affinity parameter, binding model, conformational change, and site selectivity were implemented by receptor-based and ligand-based analysis. An unusual fluorescence co-quenching (mutual quenching) was observed in the binding of IBR to HSA, followed by a static mechanism...
May 16, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29777940/curcumin-attenuates-cerebral-ischemia-injury-in-sprague-dawley-rats-and-pc12-cells-by-suppressing-overactivated-autophagy
#10
Yan Zhang, Ming Fang, Yameng Sun, Ting Zhang, Nan Shi, Jinfeng Li, Lei Jin, Kangyong Liu, Jianliang Fu
The present study assessed whether the protective effects of curcumin against cerebral ischemia injury were due to the suppression of overactivated autophagy. Curcumin is a well-known natural polyphenolic compound that effectively counteracts oxidation, inflammation, and various types of cancer. Several studies have demonstrated the protective effects of curcumin against ischemia-reperfusion injury in tissues from the lungs, cardiomyocytes, and liver. The present study employed brain injury models induced by middle cerebral artery occlusion (MCAO) in rats and PC12 oxygen-glucose-deprived (OGD) cells...
May 7, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29777928/binding-studies-of-triclocarban-with-bovine-serum-albumin-insights-from-multi-spectroscopy-and-molecular-modeling-methods
#11
Jiao Guan, Xin Yan, Yajing Zhao, Yinhe Sun, Xin Peng
The antimicrobial triclocarban (TCC) is frequently found in various personal care products (PCPs), and recent studies have demonstrated that it shows a high unintended biological activity on humans and wildlife. To evaluate the toxicity of TCC at the protein level, the effect of TCC on bovine serum albumin (BSA) has been investigated using various spectroscopic methods in combination with molecular modeling. Analysis of fluorescence quenching data of BSA revealed the formation of a ground state BSA-TCC complex with a binding constant of 2...
May 9, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29777913/the-tp53-induced-glycolysis-and-apoptosis-regulator-mediates-cooperation-between-htlv-1-p30-ii-and-the-retroviral-oncoproteins-tax-and-hbz-and-is-highly-expressed-in-an-in-vivo-xenograft-model-of-htlv-1-induced-lymphoma
#12
Tetiana Hutchison, Aditi Malu, Laçin Yapindi, Rachel Bergeson, Kendra Peck, Megan Romeo, Carolyn Harrod, Jordan Pope, Louisa Smitherman, Wesleigh Gwinn, Lee Ratner, Courtney Yates, Robert Harrod
The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ...
May 16, 2018: Virology
https://www.readbyqxmd.com/read/29777912/a-super-enhancer-maintains-homeostatic-expression-of-regnase-1
#13
Riyun Yang, Yuanyuan Wu, Yue Ming, Yuanpei Xu, Shouyan Wang, Jianbo Shen, Chenlu Wang, Xia Chen, Yongming Wang, Renfang Mao, Yihui Fan
Regnase-1 is not only a key component in maintaining intracellular homeostasis but also a critical negative regulator in preventing autoimmune diseases and cancer development. To keep homeostatic state, Regnase-1 has to be maintained at a desired level in multiple cell types. However, the molecular mechanism of keeping a certain transcriptional level of Reganase-1 is largely unknown. In this study, we found a super-enhancer (Reg-1-SE) around Regnase-1 gene is able to control the homeostatic expression of Regnase-1...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#14
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777907/novel-snps-of-wnk1-and-akr1c3-are-associated-with-preeclampsia
#15
Cheng-Juan Sun, Lin Li, Xueyan Li, Wei-Yuan Zhang, Xiao-Wei Liu
Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#16
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#17
Rahat Jahan, Muzafar A Macha, Satyanarayana Rachaghani, Srustidhar Das, Lynette M Smith, Sukhwinder Kaur, Surinder K Batra
Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest and polymorphic exon 2, along with exon 3...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777903/sox9-is-increased-in-arterial-plaque-and-stenosis-associated-with-synthetic-phenotype-of-vascular-smooth-muscle-cells-and-causes-alterations-in-extracellular-matrix-and-calcification
#18
Antje Augstein, Johannes Mierke, David M Poitz, Ruth H Strasser
Vascular smooth muscle cells (VSMC) exhibit a dual role in progression and maintenance of arteriosclerosis. They are fundamental for plaque stability but also can drive plaque progression. During pathogenic vascular remodeling, VSMC transdifferentiate into a phenotype with enhanced proliferation and migration. Moreover, they exert an increased capacity to generate extracellular matrix proteins. A special lineage of transdifferentiated VSMC expresses Sox9, a multi-functional transcription factor. The aim of the study was to examine the role of Sox9 in phenotypic alterations leading to arteriosclerosis...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777900/material-basis-research-for-huangqi-jianzhong-tang-against-chronic-atrophic-gastritis-rats-through-integration-of-urinary-metabonomics-and-systemsdock
#19
Yuetao Liu, Wenqian Xu, GuoHong Wang, Xuemei Qin
ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Jianzhong Tang (HQJZ), a celebrated traditional Chinese medicine (TCM), is commonly used for treatment of chronic atrophic gastritis (CAG) in China. AIM OF THE STUDY: We aimed to screen out the material basis of HQJZ against CAG. MATERIALS AND METHODS: CAG rat model was constructed by alternant administrations of ammonia solution and sodium deoxycholate, and the hunger disorder method. Body weight, biochemical indexes and histopathological exam were used to evaluate the efficacy of HQJZ...
May 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29777875/switching-cell-penetrating-and-cxcr4-binding-activities-of-nanoscale-organized-arginine-rich-peptides
#20
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
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