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https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#1
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777682/inhibition-of-bet-bromodomains-restores-corticosteroid-responsiveness-in-a-mixed-granulocytic-mouse-model-of-asthma
#2
Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Nahid Siddiqui, Khalid E Ibrahim, Sabry M Attia
Asthma is a heterogeneous disease characterized by different endotypes/phenotypes. Th2/Th17 driven mixed granulocytic asthma is one of them and shows resistance to corticosteroid therapy. Bromodomain and extra-terminal (BET) proteins are required for differentiation of Th17 cells which play a pivotal role in neutrophilic inflammation. Therefore, we sought to characterize the differential effects of BET inhibitor versus corticosteroids, and their potential synergism in cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model of asthma having Th2/Th17 endotype...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777585/potential-vascular-mechanisms-in-an-ex-vivo-functional-pig-bladder-model
#3
Uzoma A Anele, Paul H Ratz, Andrew F Colhoun, Sydney Roberts, Ryan Musselman, Randy A Vince, John E Speich, Adam P Klausner
AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase...
May 19, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29777503/anti-tmv-effects-of-amaryllidaceae-alkaloids-isolated-from-the-bulbs-of-lycoris-radiata-and-lycoricidine-derivatives
#4
Dong-Qiong Yang, Zhao-Rong Chen, Duo-Zhi Chen, Xiao-Jiang Hao, Shun-Lin Li
Fifteen known amaryllidaceae alkaloids were isolated from the bulbs of Lycoris radiata. Some of the compounds and lycoricidine derivatives had been screened for the activities against tobacco mosaic virus (TMV) by the conventional half-leaf method. Lycoricidine derivatives were also carried out the assay of effect on systemic infection of TMV by western-blot and RT-PCR analysis. The tested compounds showed moderate inactivation effect, whereas the lycoricidine derivatives showed good protective effect. The protective inhibitory activity of compounds L1 (N-methyl-2,3,4-trimethoxylycoricidine) (60...
May 18, 2018: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/29777398/the-role-of-dna-methylation-in-renal-cell-carcinoma
#5
REVIEW
Brittany N Lasseigne, James D Brooks
Renal cell carcinoma (RCC) is the most common kidney cancer and includes several molecular and histological subtypes with different clinical characteristics. While survival rates are high if RCC is diagnosed when still confined to the kidney and treated definitively, there are no specific diagnostic screening tests available and symptoms are rare in early stages of the disease. Management of advanced RCC has changed significantly with the advent of targeted therapies, yet survival is usually increased by months due to acquired resistance to these therapies...
May 18, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29777151/integrated-proteomics-genomics-metabolomics-approaches-reveal-oxalic-acid-as-pathogenicity-factor-in-tilletia-indica-inciting-karnal-bunt-disease-of-wheat
#6
Vishakha Pandey, Manoj Singh, Dinesh Pandey, Anil Kumar
Tilletia indica incites Karnal bunt (KB) disease in wheat. To date, no KB resistant wheat cultivar could be developed due to non-availability of potential biomarkers related to pathogenicity/virulence for screening of resistant wheat genotypes. The present study was carried out to compare the proteomes of T. indica highly (TiK) and low (TiP) virulent isolates. Twenty one protein spots consistently observed as up-regulated/differential in the TiK proteome were selected for identification by MALDI-TOF/TOF. Identified sequences showed homology with fungal proteins playing essential role in plant infection and pathogen survival, including stress response, adhesion, fungal penetration, invasion, colonization, degradation of host cell wall, signal transduction pathway...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776990/effect-of-2-psoriasis-treatments-on-vascular-inflammation-and-novel-inflammatory-cardiovascular-biomarkers-a-randomized-placebo-controlled-trial
#7
Nehal N Mehta, Daniel B Shin, Aditya A Joshi, Amit K Dey, April W Armstrong, Kristina Callis Duffin, Zelma Chiesa Fuxench, Charlotte L Harrington, Rebecca A Hubbard, Robert E Kalb, Alan Menter, Daniel J Rader, Muredach P Reilly, Eric L Simpson, Junko Takeshita, Drew A Torigian, Thomas J Werner, Andrea B Troxel, Stephen K Tyring, Suzette Baez Vanderbeek, Abby S Van Voorhees, Martin P Playford, Mark A Ahlman, Abass Alavi, Joel M Gelfand
BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins...
June 2018: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29776807/public-health-surveillance-of-multidrug-resistant-clones-of-neisseria-gonorrhoeae-in-europe-a-genomic-survey
#8
Simon R Harris, Michelle J Cole, Gianfranco Spiteri, Leonor Sánchez-Busó, Daniel Golparian, Susanne Jacobsson, Richard Goater, Khalil Abudahab, Corin A Yeats, Beatrice Bercot, Maria José Borrego, Brendan Crowley, Paola Stefanelli, Francesco Tripodo, Raquel Abad, David M Aanensen, Magnus Unemo
BACKGROUND: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data...
May 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29776758/using-preference-learning-for-detecting-inconsistencies-in-clinical-practice-guidelines-methods-and-application-to-antibiotherapy
#9
Rosy Tsopra, Jean-Baptiste Lamy, Karima Sedki
Clinical practice guidelines provide evidence-based recommendations. However, many problems are reported, such as contradictions and inconsistencies. For example, guidelines recommend sulfamethoxazole/trimethoprim in child sinusitis, but they also state that there is a high bacteria resistance in this context. In this paper, we propose a method for the semi-automatic detection of inconsistencies in guidelines using preference learning, and we apply this method to antibiotherapy in primary care. The preference model was learned from the recommendations and from a knowledge base describing the domain...
May 15, 2018: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/29776730/development-of-human-derived-hemoglobin-albumin-microspheres-as-oxygen-carriers-using-shirasu-porous-glass-membrane-emulsification
#10
Seiichi Ohta, Kenichiro Hashimoto, Xiaoting Fu, Masamichi Kamihira, Yasuyuki Sakai, Taichi Ito
Novel hemoglobin-based artificial oxygen carriers are necessary in tissue engineering. We developed human hemoglobin (hHb) and albumin (HSA)-based microspheres using Shirasu porous glass (SPG) membrane emulsification. The obtained microspheres had a uniform size with an average diameter of 15.1 μm measured by optical microscope, which is similar to the diameter of human red blood cells (7-8 μm). The loading amount of hHb in the microspheres was 20 wt%, which is similar to that of red blood cells (33 wt%)...
May 15, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#11
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29776379/development-of-a-rapid-field-applicable-molecular-diagnostic-for-knockdown-resistance-kdr-markers-in-an-gambiae
#12
Vera T Unwin, Shaun Ainsworth, Emily J Rippon, El Hadji Amadou Niang, Mark J I Paine, David Weetman, Emily R Adams
BACKGROUND: The spread of insecticide resistance (IR) is a major threat to vector control programmes for mosquito-borne diseases. Early detection of IR using diagnostic markers could help inform these programmes, especially in remote locations where gathering reliable bioassay data is challenging. Most current molecular tests for genetic IR markers are only suitable for use in well-equipped laboratory settings. There is an unmet need for field-applicable diagnostics. METHODS: A single-cartridge test was designed to detect key IR mutations in the major African vector of malaria, Anopheles gambiae...
May 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#13
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29776333/transcriptomic-analysis-of-genes-in-soybean-in-response-to-peronospora-manshurica-infection
#14
Hang Dong, Shuangfeng Shi, Chong Zhang, Sihui Zhu, Mei Li, Jie Tan, Yue Yu, Liping Lin, Shirong Jia, Xujing Wang, Yuanhua Wu, Yuhui Liu
BACKGROUND: Soybean downy mildew (SDM), caused by Peronospora manshurica (Pm), is a major fungal disease in soybean. To date, little is known regarding the defense mechanism at molecular level and how soybean plants response to Pm infection. In this study, differential gene expression in SDM-resistant (HR) and SDM-susceptible (HS) genotype was analyzed by RNA-seq to identify differentially expressed genes (DEGs) following Pm infection. RESULTS: Of a total of 55,017 genes mapped to the soybean reference genome sequences, 2581 DEGs were identified...
May 18, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29775863/superoxide-o-2-accumulation-contributes-to-symptomless-type-i-nonhost-resistance-of-plants-to-biotrophic-pathogens
#15
András Künstler, Renáta Bacsó, Réka Albert, Balázs Barna, Zoltán Király, Yaser Mohamed Hafez, József Fodor, Ildikó Schwarczinger, Lóránt Király
Nonhost resistance is the most common form of disease resistance exhibited by plants against most pathogenic microorganisms. Type I nonhost resistance is symptomless (i.e. no macroscopically visible cell/tissue death), implying an early halt of pathogen growth. The timing/speed of defences is much more rapid during type I nonhost resistance than during type II nonhost and host ("gene-for-gene") resistance associated with a hypersensitive response (localized necrosis, HR). However, the mechanism(s) underlying symptomless (type I) nonhost resistance is not entirely understood...
May 7, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29775814/composite-self-expanding-bioresorbable-prototype-stents-with-reinforced-compression-performance-for-congenital-heart-disease-application-computational-and-experimental-investigation
#16
Fan Zhao, Wen Xue, Fujun Wang, Laijun Liu, Haoqin Shi, Lu Wang
Stents are vital devices to treat vascular stenosis in pediatric patients with congenital heart disease. Bioresorbable stents (BRSs) have been applied to reduce challenging complications caused by permanent metal stents. However, it remains almost a total lack of BRSs with satisfactory compression performance specifically for children with congenital heart disease, leading to importantly suboptimal effects. In this work, composite bioresorbable prototype stents with superior compression resistance were designed by braiding and annealing technology, incorporating poly (p-dioxanone) (PPDO) monofilaments and polycaprolactone (PCL) multifilament...
May 8, 2018: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29775748/microrna-204-5p-regulates-3t3-l1-preadipocyte-proliferation-apoptosis-and-differentiation
#17
Jingjing Du, Peiwen Zhang, Mailin Gan, Xue Zhao, Yan Xu, Qiang Li, Yanzhi Jiang, Guoqing Tang, Mingzhou Li, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
Obesity due to excessive lipid accumulation is closely associated with metabolic diseases such as type 2 diabetes, insulin resistance and inflammation. Therefore, a detailed understanding of the molecular mechanisms that underlie adipogenesis is crucial to develop treatments for diseases related to obesity. Here, we found that the microRNA-204-5p (miR-204-5p) was expressed at low levels in fat tissues from obese mice fed long-term with a high-fat diet (HFD). Overexpression or inhibition of miR-204-5p in vitro in 3T3-L1 preadipocytes significantly inhibited or promoted 3T3-L1 proliferation, respectively, an effect mediated by regulating cell proliferation factors...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775494/osa-mir164a-targets-osnac60-and-negatively-regulates-rice-immunity-against-the-blast-fungus-magnaporthe-oryzae
#18
Zhaoyun Wang, Yeqiang Xia, Siyuan Lin, Yanru Wang, Baohuan Guo, Xiaoning Song, Shaochen Ding, Liyu Zheng, Ruiying Feng, Shulin Chen, Yalin Bao, Cong Sheng, Xin Zhang, Jianguo Wu, Dongdong Niu, Hailing Jin, Hongwei Zhao
Exploring the regulatory mechanism played by endogenous rice miRNAs in defense responses against the blast disease is of great significance in both resistant variety breeding and disease control management. We identified rice defense-related miRNAs by comparing rice miRNA expression patterns before and after Magnaporthe oryzae strain Guy11 infection. We discovered that osa-miR164a expression reduced upon Guy11 infection at both early and late stages, which was perfectly associated with the induced expression of its target gene, OsNAC60...
May 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29775474/the-cryptococcus-neoformans-titan-cell-is-an-inducible-and-regulated-morphotype-underlying-pathogenesis
#19
Ivy M Dambuza, Thomas Drake, Ambre Chapuis, Xin Zhou, Joao Correia, Leanne Taylor-Smith, Nathalie LeGrave, Tim Rasmussen, Matthew C Fisher, Tihana Bicanic, Thomas S Harrison, Marcel Jaspars, Robin C May, Gordon D Brown, Raif Yuecel, Donna M MacCallum, Elizabeth R Ballou
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29775454/in-vivo-and-in-vitro-studies-of-cry5b-and-nicotinic-acetylcholine-receptor-agonist-anthelmintics-reveal-a-powerful-and-unique-combination-therapy-against-intestinal-nematode-parasites
#20
Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K Nielsen, Raffi V Aroian
BACKGROUND: The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate...
May 18, 2018: PLoS Neglected Tropical Diseases
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