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https://www.readbyqxmd.com/read/28231271/applying-antibody-sensitive-hypervariable-region-1-deleted-hepatitis-c-virus-to-the-study-of-escape-pathways-of-neutralizing-human-monoclonal-antibody-ar5a
#1
Rodrigo Velázquez-Moctezuma, Mansun Law, Jens Bukh, Jannick Prentoe
Hepatitis C virus (HCV) is a major cause of end-stage liver diseases. With 3-4 million new HCV infections yearly, a vaccine is urgently needed. A better understanding of virus escape from neutralizing antibodies and their corresponding epitopes are important for this effort. However, for viral isolates with high antibody resistance, or antibodies with moderate potency, it remains challenging to induce escape mutations in vitro. Here, as proof-of-concept, we used antibody-sensitive HVR1-deleted (ΔHVR1) viruses to generate escape mutants for a human monoclonal antibody, AR5A, targeting a rare cross-genotype conserved epitope...
February 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28230992/novel-design-of-heptad-amphiphiles-to-enhance-cell-selectivity-salt-resistance-anti-biofilm-properties-and-their-membrane-disruptive-mechanism
#2
Xiujing Dou, Xin Zhu, Jiajun Wang, Na Dong, Anshan Shan
Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile's helical propensity and cell selectivity...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#3
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230771/antibiotic-resistance-determinant-focused-acinetobacter-baumannii-vaccine-designed-using-reverse-vaccinology
#4
Zhaohui Ni, Yan Chen, Edison Ong, Yongqun He
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230733/ck2-molecular-targeting-tumor-cell-specific-delivery-of-rnai-in-various-models-of-cancer
#5
REVIEW
Janeen H Trembley, Betsy T Kren, Md Joynal Abedin, Rachel I Vogel, Claire M Cannon, Gretchen M Unger, Khalil Ahmed
Protein kinase CK2 demonstrates increased protein expression relative to non-transformed cells in the majority of cancers that have been examined. The elevated levels of CK2 are involved in promoting not only continued proliferation of cancer cells but also their resistance to cell death; thus, CK2 has emerged as a plausible target for cancer therapy. Our focus has been to target CK2 catalytic subunits at the molecular level using RNA interference (RNAi) strategies to achieve their downregulation. The delivery of oligonucleotide therapeutic agents warrants that they are protected and are delivered specifically to cancer cells...
February 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230606/secretions-of-bifidobacterium-infantis-and-lactobacillus-acidophilus-protect-intestinal-epithelial-barrier-function
#6
Shuangshuang Guo, Tyler Gillingham, Yuming Guo, Di Meng, Weishu Zhu, W Allen Walker, Kriston Ganguli
OBJECTIVES: The secreted metabolites of probiotics are cytoprotective to intestinal epithelium and have been shown to attenuate inflammation and reduce gut permeability. The present study was designed to determine the protective effects of probiotic conditioned media (PCM) from Bifidobacterium infantis (BCM) and Lactobacillus acidophilus (LCM) on interleukin (IL)-1β-induced intestinal barrier compromise. METHODS: The epithelial barrier was determined by measuring the transepithelial electrical resistance (TER) across a Caco-2 cell monolayer using a Transwell model...
March 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28230086/classification-of-idiopathic-interstitial-pneumonias-using-anti-myxovirus-resistance-protein-1-autoantibody
#7
Yoshimasa Hamano, Hiroshi Kida, Shoichi Ihara, Akihiro Murakami, Masahiro Yanagawa, Ken Ueda, Osamu Honda, Lokesh P Tripathi, Toru Arai, Masaki Hirose, Toshimitsu Hamasaki, Yukihiro Yano, Tetsuya Kimura, Yasuhiro Kato, Hyota Takamatsu, Tomoyuki Otsuka, Toshiyuki Minami, Haruhiko Hirata, Koji Inoue, Izumi Nagatomo, Yoshito Takeda, Masahide Mori, Hiroyoshi Nishikawa, Kenji Mizuguchi, Takashi Kijima, Masanori Kitaichi, Noriyuki Tomiyama, Yoshikazu Inoue, Atsushi Kumanogoh
Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#8
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28229585/plasma-induced-decomposition-of-copper-complex-ink-for-the-formation-of-highly-conductive-copper-tracks-on-heat-sensitive-substrates
#9
Yousef Farraj, Ariel Smooha, Alexander Kamyshny, Shlomo Magdassi
The use of Cu-formate-AMP ink and low-pressure plasma for the formation of highly conductive patterns on heat sensitive plastic substrates, were studied. It was found that plasma results in decomposition of copper complex to form metallic copper without heating at high temperatures. Ink composition and plasma parameters (pre-drying conditions, plasma treatment duration, gas type and flow rate) were optimized to obtain uniform conductive metallic films. The morphology and electrical characteristics of these films were evaluated...
February 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#10
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28229333/production-of-conidia-by-entomopathogenic-fungi-from-inoculants-to-final-quality-tests
#11
REVIEW
Facundo Muñiz-Paredes, Francisco Miranda-Hernández, Octavio Loera
Demand for biopesticides is growing due to the increase of areas under integrated pest management worldwide. Conidia from entomopathogenic fungi play a major role as infective units in the current market of biopesticides. Success in a massive production of fungal conidia include the use of proper long-term conservation microbial methods, aimed at preserving the phenotypic traits of the strains. The development of suitable inoculants should also be considered since that favours a rapid germination and invasiveness of the substrate in solid state cultures (SSC)...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28229230/mycobacterium-ulcerans-mycolactone-interferes-with-adhesion-migration-and-proliferation-of-primary-human-keratinocytes-and-hacat-cell-line
#12
Francesca Graziola, Elena Colombo, Rossana Tiberio, Giorgio Leigheb, Chiarella Bozzo
The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactone has been linked to its apoptogenic activity. We explored if low mycolactone concentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocyte populations, keratinocyte stem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyte line, HaCaT. We demonstrated that 0.01 and 0...
February 22, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28229139/pti2-dach-the-iodido-analogue-of-oxaliplatin-as-a-candidate-for-colorectal-cancer-treatment-chemical-and-biological-features
#13
D Cirri, S Pillozzi, C Gabbiani, J Tricomi, G Bartoli, M Stefanini, E Michelucci, A Arcangeli, L Messori, T Marzo
Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides...
February 23, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28228846/decoupling-the-downstream-effects-of-germline-nuclear-rnai-reveals-that-h3k9me3-is-dispensable-for-heritable-rnai-and-the-maintenance-of-endogenous-sirna-mediated-transcriptional-silencing-in-caenorhabditis-elegans
#14
Natallia Kalinava, Julie Zhouli Ni, Kimberly Peterman, Esteban Chen, Sam Guoping Gu
BACKGROUND: Germline nuclear RNAi in C. elegans is a transgenerational gene-silencing pathway that leads to H3K9 trimethylation (H3K9me3) and transcriptional silencing at the target genes. H3K9me3 induced by either exogenous double-stranded RNA (dsRNA) or endogenous siRNA (endo-siRNA) is highly specific to the target loci and transgenerationally heritable. Despite these features, the role of H3K9me3 in siRNA-mediated transcriptional silencing and inheritance of the silencing state at native target genes is unclear...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28228728/perivascular-adipose-tissue-s-impact-on-norepinephrine-induced-contraction-of-mesenteric-resistance-arteries
#15
Nadia Ayala-Lopez, Janice M Thompson, Stephanie W Watts
Background: Perivascular adipose tissue (PVAT) can decrease vascular contraction to NE. We tested the hypothesis that metabolism and/or uptake of vasoactive amines by mesenteric PVAT (MPVAT) could affect NE-induced contraction of the mesenteric resistance arteries. Methods: Mesenteric resistance vessels (MRV) and MPVAT from male Sprague-Dawley rats were used. RT-PCR and Western blots were performed to detect amine metabolizing enzymes. The Amplex® Red Assay was used to quantify oxidase activity by detecting the oxidase reaction product H2O2 and the contribution of PVAT on the mesenteric arteries' contraction to NE was measured by myography...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28228268/er-stress-protein-chop-mediates-insulin-resistance-by-modulating-adipose-tissue-macrophage-polarity
#16
Toru Suzuki, Junhong Gao, Yasushi Ishigaki, Keiichi Kondo, Shojiro Sawada, Tomohito Izumi, Kenji Uno, Keizo Kaneko, Sohei Tsukita, Kei Takahashi, Atsuko Asao, Naoto Ishii, Junta Imai, Tetsuya Yamada, Seiichi Oyadomari, Hideki Katagiri
Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into white adipose tissue (WAT), thereby inducing insulin resistance. Herein, we demonstrate the importance of an ER stress protein, CHOP, in determining adipose tissue macrophage (ATM) polarity and systemic insulin sensitivity. A high-fat diet (HFD) enhances ER stress with CHOP upregulation in adipocytes. CHOP deficiency prevents HFD-induced insulin resistance and glucose intolerance with ATM M2 predomination and Th2 cytokine upregulation in WAT...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228262/targeting-dna-damage-response-in-prostate-cancer-by-inhibiting-androgen-receptor-cdc6-atr-chk1-signaling
#17
Styliani Karanika, Theodoros Karantanos, Likun Li, Jianxiang Wang, Sanghee Park, Guang Yang, Xuemei Zuo, Jian H Song, Sankar N Maity, Ganiraju C Manyam, Bradley Broom, Ana M Aparicio, Gary E Gallick, Patricia Troncoso, Paul G Corn, Nora Navone, Wei Zhang, Shuhua Li, Timothy C Thompson
Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228218/-thioridazine-sensitizes-apoptotic-effect-of-trail-in-human-lung-cancer-pc9-cells-through-er-stress-mediated-up-regulation-of-dr5
#18
Juan Li, Yi Wang, Liu Liu, Yuan Yuan, Yangyi Bao
BACKGROUND: Tumor necrosis factor-related apoptosis-inducting ligand (TRAIL) can induce apoptosis of tumor cells, however, various of tumor cells may survive because of resistance to TRAIL-mediated apoptosis. This study is to observe the proliferation inhibition effect of TRAIL sensitized by thioridazine on PC9 cells through endoplasmic reticulum (ER) stress mediated up-regulation of death receptor 5 (DR5) and investigate its mechanism. METHODS: PC9 cells were treated with different concentrations of thioridazine and TRAIL alone or in combination...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28228057/intravenous-chlorothiazide-versus-enteral-metolazone-to-augment-loop-diuretic-therapy-in-the-intensive-care-unit
#19
Christopher J Michaud, Kendall C Mintus
BACKGROUND: In cases of loop diuretic resistance in the intensive care unit (ICU), recommendations for a specific second-line thiazide agent are lacking. OBJECTIVE: To compare the effects of intravenous chlorothiazide (CTZ) and enteral metolazone (MET) on urine output (UOP) when added to furosemide monotherapy therapy in critically ill adults. METHODS: This was a retrospective cohort study conducted in the medical, surgical, and cardiothoracic ICUs of a quaternary medical center...
April 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#20
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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