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https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#1
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28088073/strategies-to-design-clinical-studies-to-identify-predictive-biomarkers-in-cancer-research
#2
REVIEW
Jose Luis Perez-Gracia, Miguel F Sanmamed, Ana Bosch, Ana Patiño-Garcia, Kurt A Schalper, Victor Segura, Joaquim Bellmunt, Josep Tabernero, Christopher J Sweeney, Toni K Choueiri, Miguel Martín, Juan Pablo Fusco, Maria Esperanza Rodriguez-Ruiz, Alfonso Calvo, Celia Prior, Luis Paz-Ares, Ruben Pio, Enrique Gonzalez-Billalabeitia, Alvaro Gonzalez Hernandez, David Páez, Jose María Piulats, Alfonso Gurpide, Mapi Andueza, Guillermo de Velasco, Roberto Pazo, Enrique Grande, Pilar Nicolas, Francisco Abad-Santos, Jesus Garcia-Donas, Daniel Castellano, María J Pajares, Cristina Suarez, Ramon Colomer, Luis M Montuenga, Ignacio Melero
The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers...
December 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#3
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087761/proteomics-technologies-and-their-applications
#4
REVIEW
Bilal Aslam, Madiha Basit, Muhammad Atif Nisar, Mohsin Khurshid, Muhammad Hidayat Rasool
Proteomics involves the applications of technologies for the identification and quantification of overall proteins present content of a cell, tissue or an organism. It supplements the other "omics" technologies such as genomic and transcriptomics to expound the identity of proteins of an organism, and to cognize the structure and functions of a particular protein. Proteomics-based technologies are utilized in various capacities for different research settings such as detection of various diagnostic markers, candidates for vaccine production, understanding pathogenicity mechanisms, alteration of expression patterns in response to different signals and interpretation of functional protein pathways in different diseases...
February 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/28087756/fine-mapping-of-genes-determining-extrafusal-fiber-properties-in-murine-soleus-muscle
#5
Andrew Carroll, Riyan Cheng, Elaina Collie-Duguid, Caroline Meharg, Michael E Scholz, Steven N Fiering, Jennifer L Fields, Abraham A Palmer, Arimantas Lionikas
INTRODUCTION: Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits, however, the underlying genes remain poorly understood. AIMS: This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains. METHODS: Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped male and female mice of the F34 generation of advanced intercross lines (AIL) derived from the LG/J and SM/J strains...
January 13, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28087735/relationships-linking-emotional-motor-cognitive-and-gabaergic-dysfunctions-in-dystrophin-deficient-mdx-mice
#6
Cyrille Vaillend, Rémi Chaussenot
Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central GABAA receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087653/identification-of-regulatory-networks-and-hub-genes-controlling-soybean-seed-set-and-size-using-rna-sequencing-analysis
#7
Juan Du, Shoudong Wang, Cunman He, Bin Zhou, Yong-Ling Ruan, Huixia Shou
To understand the gene expression networks controlling soybean seed set and size, transcriptome analyses were performed in three early seed developmental stages, using two genotypes with contrasting seed size. The two-dimensional data set provides a comprehensive and systems-level view on dynamic gene expression networks underpinning soybean seed set and subsequent development. Using pairwise comparisons and weighted gene coexpression network analyses, we identified modules of coexpressed genes and hub genes for each module...
January 13, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28087594/a-human-proteome-array-approach-to-identifying-key-host-proteins-targeted-by-toxoplasma-kinase-rop18
#8
Zhaoshou Yang, Yongheng Hou, Taofang Hao, Hee-Sool Rho, Jun Wan, Yizhao Luan, Xin Gao, Jianping Yao, Aihua Pan, Zhi Xie, Jiang Qian, Wanqin Liao, Heng Zhu, Xingwang Zhou
Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty-eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087576/circulating-modified-metabolites-and-a-risk-of-esrd-in-patients-with-type-1-diabetes-and-chronic-kidney-disease
#9
Monika A Niewczas, Anna V Mathew, Stephanie Croall, Jaeman Byun, Melissa Major, Venkatta S Sabisetti, Adam Smiles, Joseph V Bonventre, Subramaniam Pennathur, Andrzej S Krolewski
OBJECTIVE: Patients with type 1 diabetes (T1D) with impaired renal function are at increased risk for end-stage renal disease (ESRD). Although the rate of progression varies, determinants and mechanisms of this variation are unknown. RESEARCH DESIGN AND METHODS: We examined serum metabolomic profiles associated with variation in renal function decline in participants with T1D (the Joslin Kidney Study prospective cohort). One hundred fifty-eight patients with proteinuria and chronic kidney disease stage 3 were followed for a median of 11 years to determine estimated glomerular filtration rate slopes from serial measurements of serum creatinine and to ascertain time to onset of ESRD...
January 13, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28087566/application-of-whole-exome-sequencing-in-the-clinical-diagnosis-and-management-of-inherited-cardiovascular-diseases-in-adults
#10
Sara B Seidelmann, Emily Smith, Lakshman Subrahmanyan, Daniel Dykas, Maen D Abou Ziki, Bani Azari, Fady Hannah-Shmouni, Yuexin Jiang, Joseph G Akar, Mark Marieb, Daniel Jacoby, Allen E Bale, Richard P Lifton, Arya Mani
BACKGROUND: With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated. METHODS AND RESULTS: We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28087530/pgas-a-low-ph-induced-promoter-as-a-dynamic-gene-expression-control-tool-for-the-metabolic-engineering-of-aspergillus-niger
#11
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
: The dynamic control of gene expression is important for adjusting fluxes in order to obtain desired products and achieve appropriate cell growth, particularly when the synthesis of a desired product drains metabolites required for cell growth. For dynamic gene expression, a promoter responsive to a particular environmental stressor is vital. Here, we report a low pH-inducible promoter, Pgas, which promotes minimal gene expression at pH values of greater than 5.0, but functioned efficiently at low pH values, such as pH 2...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087464/mitochondrial-reactive-oxygen-species-regulate-fungal-protease-induced-inflammatory-responses
#12
Yun Hee Kim, Seung-Hyo Lee
Epidemiological studies have shown that fungal infections are a main cause of respiratory tract diseases, such as asthma, bronchopneumonia, intoxication, and invasive fungal disease. Fungi such as Aspergillus and Candida species have become increasingly important pathogens as the global climate changes. Accordingly, in this study, we evaluated the toxicological potential of Aspergillus protease in the lower respiratory tract. Exposure of Aspergillus protease to A549 cells induced upregulation of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 mRNAs and increased production of interleukin (IL)-8 and MCP-1 protein through enhanced mitochondrial reactive oxygen species (ROS) generation and activation of mitogen-activated protein kinase (MAPK) and activator protein (AP)-1...
January 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28087369/multidimensional-assessment-of-impulsivity-in-relation-to-obesity-and-food-addiction
#13
Lauren VanderBroek-Stice, Monika K Stojek, Steven R H Beach, Michelle R vanDellen, James MacKillop
Based on similarities between overconsumption of food and addictive drugs, there is increasing interest in "food addiction," a compulsive eating pattern defined using symptoms parallel to substance use disorders. Impulsivity, a multidimensional construct robustly linked to drug addiction, has been increasingly examined as an obesity determinant, but with mixed findings. This study sought to clarify relations between three major domains of impulsivity (i.e., impulsive personality traits, discounting of delayed rewards, and behavioral inhibition) in both obesity and food addiction...
January 10, 2017: Appetite
https://www.readbyqxmd.com/read/28087360/the-synthetic-peptide-pnpp-19-induces-peripheral-antinociception-via-activation-of-no-cgmp-katp-pathway-role-of-enos-and-nnos
#14
A C N Freitas, G Silva, D F Pacheco, V Lemos, I D G Duarte, M E de Lima
BACKGROUND AND PURPOSE: The peptide PnPP-19, derived from the spider toxin PnTx2-6, potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 μg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels...
January 10, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#15
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28087313/an-m2-v27a-channel-blocker-demonstrates-potent-in-vitro-and-in-vivo-antiviral-activities-against-amantadine-sensitive-and-resistant-influenza-a-viruses
#16
Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F Smee, William F DeGrado, Jun Wang
Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target...
January 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087289/clinical-utility-and-functional-analysis-of-variants-in-atrial-fibrillation-associated-locus-4q25
#17
Yusuke Ebana, Kouichi Ozaki, Lian Liu, Hitoshi Hachiya, Kenzo Hirao, Mitsuaki Isobe, Michiaki Kubo, Toshihiro Tanaka, Tetsushi Furukawa
BACKGROUND: Chromosome 4q25 has been repeatedly identified as atrial fibrillation (AF)-sensitive locus in multiple genome-wide association studies (GWAS) and is considered to hold some clues to AF pathogenesis. We aimed to investigate the clinical utilities in Japanese and to unveil the function of the 4q25 locus in affecting transcription of adjacent genes. METHODS: We conducted AF GWAS in Japanese population (1382 AF cases and 1478 controls) and the replication panel (1666 AF cases and 1229 controls) with detailed clinical information which showed the acceleration of AF onset...
January 10, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28087277/identification-of-ubact-a-ubiquitin-like-protein-along-with-other-homologous-components-of-a-conjugation-system-and-the-proteasome-in-different-gram-negative-bacteria
#18
Gilad Lehmann, Ronald G Udasin, Ido Livneh, Aaron Ciechanover
Systems analogous to the eukaryotic ubiquitin-proteasome system have been previously identified in Archaea, and Actinobacteria (gram-positive), but not in gram-negative bacteria. Here, we report the bioinformatic identification of a novel prokaryotic ubiquitin-like protein, which we name UBact. The phyletic distribution of UBact covers at least five gram-negative bacterial phyla, including Nitrospirae, Armatimonadetes, Verrucomicroba, Nitrospinae, and Planctomycetes. Additionally, it was identified in seven candidate (uncultured) phyla and one Archaeon...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087272/synthesis-and-evaluation-of-5-1h-indol-3-yl-n-aryl-1-3-4-oxadiazol-2-amines-as-bcl-2-inhibitory-anticancer-agents
#19
Rania Hamdy, Noha I Ziedan, Samia Ali, Cinzia Bordoni, Mohamed El-Sadek, Elsaid Lashin, Andrea Brancale, Arwyn T Jones, Andrew D Westwell
A series of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines 8a-j has been designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents based on our previous lead compound 8a. Synthesis of the target compounds was readily accomplished through a cyclisation reaction between indole-3-carboxylic acid hydrazide (5) and substituted isothiocyanates 6a-j, followed by oxidative cyclodesulfurization of the corresponding thiosemicarbazide 7a-j using 1,3-dibromo-5,5-dimethylhydantoin...
December 27, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28087261/dna-aptamer-probes-for-detection-of-estrogen-receptor-%C3%AE-positive-carcinomas
#20
Arghya Sett, Bibhuti Bhusan Borthakur, Jagannath Dev Sharma, Amal Chandra Kataki, Utpal Bora
Estrogen receptor alpha (ERα) which is a ligand-activated transcription factor also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1). It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. The enriched aptamer candidate was obtained after 14 iterative cycles of in vitro protein-SELEX process. Isothermal calorimetry study suggests the nanomolar sensitivity of the candidate ER_Apt1 to its target protein...
December 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
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