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https://www.readbyqxmd.com/read/29935436/tuning-b-cell-responses-to-antigens-by-cell-polarity-and-membrane-trafficking
#1
Felipe Del Valle Batalla, Ana-María Lennon-Dumenil, María-Isabel Yuseff
The capacity of B lymphocytes to produce specific antibodies, particularly broadly neutralizing antibodies that provide immunity to viral pathogens has positioned them as valuable therapeutic targets for immunomodulation. To become competent as antibody secreting cells, B cells undergo a series of activation steps, which are triggered by the recognition of antigens frequently displayed on the surface of other presenting cells. Such antigens elicit the formation of an immune synapse (IS), where local cytoskeleton rearrangements coupled to mechanical forces and membrane trafficking orchestrate the extraction and processing of antigens in B cells...
June 20, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29935346/ethnopharmacology-phytochemistry-and-pharmacology-of-chinese-salvia-species-a-review
#2
REVIEW
Xu Jianping, Wei Kunhua, Zhang Guojun, Lei Lujing, Yang Dawei, Wang Wenle, Han Qiheng, Xia Yuan, Bi Yaqiong, Yang Min, Li Minhui
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Salvia is one of the largest genera of the Lamiaceae family. In China, about 40 Salvia species have been used as medicinal plants for treatment of various diseases, specifically hepatic and renal diseases and those of the cardiovascular and immune systems. AIM OF THIS REVIEW: This review aims to provide systematically organized information on the ethnopharmacology, phytochemistry, pharmacology, and toxicology of medicinal Salvia species in China to support their therapeutic potential in the treatment of human diseases...
June 20, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29935345/the-a-z-of-zika-drug-discovery
#3
REVIEW
Melina Mottin, Joyce V V B Borba, Rodolpho C Braga, Pedro H M Torres, Matheus C Martini, Jose Luiz Proenca-Modena, Carla C Judice, Fabio T M Costa, Sean Ekins, Alexander L Perryman, Carolina Horta Andrade
Despite the recent outbreak of Zika virus (ZIKV), there are still no approved treatments, and early-stage compounds are probably many years away from approval. A comprehensive A-Z review of the recent advances in ZIKV drug discovery efforts is presented, highlighting drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets are also described and discussed, as well as targets belonging to the host cell, as new opportunities for ZIKV drug discovery...
June 20, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29935311/molecular-pathway-activation-new-type-of-biomarkers-for-tumor-morphology-and-personalized-selection-of-target-drugs
#4
REVIEW
Anton Buzdin, Maxim Sorokin, Andrew Garazha, Marina Sekacheva, Ella Kim, Nikolay Zhukov, Ye Wang, Xinmin Li, Souvik Kar, Christian Hartmann, Amir Samii, Alf Giese, Nicolas Borisov
Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient...
June 20, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29935185/inhibition-of-microrna-16-facilitates-the-paclitaxel-resistance-by-targeting-ikbkb-via-nf-%C3%AE%C2%BAb-signaling-pathway-in-hepatocellular-carcinoma
#5
Yingbin Huang, Guangyu Chen, Yang Wang, Rui He, Jun Du, Xingyuan Jiao, Qiang Tai
Hepatocellular carcinoma (HCC) is a common malignant tumor usually resistant to chemotherapy. MicroRNAs play important roles in modulation of carcinogenesis and chemoresistance, which miR-16 has been reported to mediate chemoresistance in many types of cancers. However, the role of miR-16 in HCC remains unknown. The aim of this study was to investigate whether miR-16 is participated in chemoresistance in HCC and shed light on the underlying molecular mechanisms. The findings of the current study discover that miR-16 is down-regulated in HCC tissue and cell lines...
June 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29935182/rna-interference-in-vivo-in-schistosoma-japonicum-establishing-and-optimization-of-rnai-mediated-suppression-of-gene-expression-by-long-dsrna-in-the-intra-mammalian-life-stages-of-worms
#6
Jian Li, Manyu Xiang, Ruixiang Zhang, Bin Xu, Wei Hu
Schistosomes are parasitic platyhelminths that threaten over 600 million people globally. In recent years, RNA interference (RNAi) has been widely used as a molecular tool in research into the genomic function of parasites. We aim to develop effective protocols for application of RNAi technology in the intra-mammalian life stages of Schistosoma japonicum. In this work, the expression of the parasite gene encoding cathepsin B1 (SjCB1) was targeted by exposing the worms to 10 μg of long dsRNA dissolved in 0...
June 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29935175/targeting-vascular-inflammation-in-ischemic-stroke-recent-developments-on-novel-immunomodulatory-approaches
#7
Shashank Shekhar, Mark W Cunningham, Mallikarjuna R Pabbidi, Shaoxun Wang, George W Booz, Fan Fan
Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment...
June 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29935173/nucleic-acid-based-gene-therapy-approaches-for-sepsis
#8
Yuichi Hattori, Kohshi Hattori, Tokiko Suzuki, Sailesh Palikhe, Naoyuki Matsuda
Despite advances in overall medical care, sepsis and its sequelae continue to be an embarrassing clinical entity with an unacceptably high mortality rate. The central reason for high morbidity and high mortality of sepsis and its sequelae is the lack of an effective treatment. Previous clinical trials have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Thus, the key goal favoring the outcome of septic patients is to devise innovative and evolutionary therapeutic strategies...
June 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29935171/targeting-formyl-peptide-receptors-to-facilitate-the-resolution-of-inflammation
#9
János G Filep, Meriem Shekeri, Driss El Kebir
The formyl peptide receptors (FPRs) are G protein coupled receptors that recognize a broad range of structurally distinct pathogen and danger-associated molecular patterns and mediate host defense to infection and tissue injury. It became evident that the cellular distribution and biological functions of FPRs extend beyond myeloid cells and governing their activation and trafficking. In recent years, significant progress has been made to position FPRs at check points that control the resolution of inflammation, tissue repair and return to homeostasis...
June 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29934897/approaching-pharmacological-space-events-and-components
#10
Giulio Vistoli, Alessandro Pedretti, Angelica Mazzolari, Bernard Testa
With a view to introducing the concept of pharmacological space and its potential applications in investigating and predicting the toxic mechanisms of xenobiotics, this opening chapter describes the logical relations between conformational behavior, physicochemical properties and binding spaces, which are seen as the three key elements composing the pharmacological space. While the concept of conformational space is routinely used to encode molecular flexibility, the concepts of property spaces and, particularly, of binding spaces are more innovative...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29934893/molecular-docking-for-predictive-toxicology
#11
Daniela Trisciuzzi, Domenico Alberga, Francesco Leonetti, Ettore Novellino, Orazio Nicolotti, Giuseppe F Mangiatordi
Molecular docking is an in silico method widely applied in drug discovery programs to predict the binding mode of a given molecule interacting with a specific biological target. This computational technique is today emerging also in the field of predictive toxicology for regulatory purposes, being for instance successfully applied to develop classification models for the prediction of the endocrine disruptor potential of chemicals. Herein, we describe the protocol for adapting molecular docking to the purposes of predictive toxicology...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29934785/tackling-maize-fusariosis-in-search-of-fusarium-graminearum-biosuppressors
#12
Adetomiwa Ayodele Adeniji, Olubukola Oluranti Babalola
This review presents biocontrol agents employed to alleviate the deleterious effect of the pathogen Fusarium graminearum on maize. The control of this mycotoxigenic phytopathogen remains elusive despite the elaborate research conducted on its detection, identification, and molecular fingerprinting. This could be attributed to the fact that in vitro and greenhouse biocontrol studies on F. graminearum have exceeded the number of field studies done. Furthermore, along with the variances seen among these F. graminearum suppressing biocontrol strains, it is also clear that the majority of research done to tackle F...
June 22, 2018: Archives of Microbiology
https://www.readbyqxmd.com/read/29934776/silencing-of-mir156-confers-enhanced-resistance-to-brown-planthopper-in-rice
#13
Yafei Ge, Junyou Han, Guoxin Zhou, Yunmin Xu, Yue Ding, Min Shi, Changkui Guo, Gang Wu
Silencing of miR156 in rice confers enhanced resistance to brown planthopper through reducing JA and JA-Ile biosynthesis. Rice brown planthopper (BPH, Nilaparvata lugens Stål) threatens the sustainability of rice production and global food security. Due to the rapid adaptation of BPH to current germplasms in rice, development of novel types of resistant germplasms becomes increasingly important. Plant ontogenetic defense against pathogen and herbivores offers a broad spectrum and durable resistance, and has been experimentally tested in many plants; however, the underlying molecular mechanism remains unclear...
June 22, 2018: Planta
https://www.readbyqxmd.com/read/29934750/quantitative-surface-field-analysis-learning-causal-models-to-predict-ligand-binding-affinity-and-pose
#14
Ann E Cleves, Ajay N Jain
We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone. The method is closely related to the QMOD approach, substituting a learned scoring field for a pocket constructed of molecular fragments. The problem of mutual ligand alignment is addressed in a general way, and optimal model parameters and ligand poses are identified through multiple-instance machine learning. We provide algorithmic details along with performance results on sixteen structure-activity data sets covering many pharmaceutically relevant targets...
June 22, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29934689/e3-ubiquitin-ligase-c-cbl-inhibits-microglia-activation-after-chronic-constriction-injury
#15
Pengfei Xue, Xiaojuan Liu, Yiming Shen, Yuanyuan Ju, Xiongsong Lu, Jinlong Zhang, Guanhua Xu, Yuyu Sun, Jiajia Chen, Haiyan Gu, Zhiming Cui, Guofeng Bao
E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway...
June 22, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29934580/expression-ratio-of-the-tgf%C3%AE-inducible-gene-myo10-is-prognostic-for-overall-survival-of-squamous-cell-lung-cancer-patients-and-predicts-chemotherapy-response
#16
D Dvornikov, M A Schneider, S Ohse, M Szczygieł, I Titkova, M Rosenblatt, T Muley, A Warth, F J Herth, H Dienemann, M Thomas, J Timmer, M Schilling, H Busch, M Boerries, M Meister, U Klingmüller
In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes...
June 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29934564/accelerating-the-discovery-of-insensitive-high-energy-density-materials-by-a-materials-genome-approach
#17
Yi Wang, Yuji Liu, Siwei Song, Zhijian Yang, Xiujuan Qi, Kangcai Wang, Yu Liu, Qinghua Zhang, Yong Tian
Finding new high-energy-density materials with desired properties has been intensely-pursued in recent decades. However, the contradictory relationship between high energy and low mechanical sensitivity makes the innovation of insensitive high-energy-density materials an enormous challenge. Here, we show how a materials genome approach can be used to accelerate the discovery of new insensitive high-energy explosives by identification of "genetic" features, rapid molecular design, and screening, as well as experimental synthesis of a target molecule, 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide...
June 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29934502/precision-therapeutic-targeting-of-human-cancer-cell-motility
#18
Li Xu, Ryan Gordon, Rebecca Farmer, Abhinandan Pattanayak, Andrew Binkowski, Xiaoke Huang, Michael Avram, Sankar Krishna, Eric Voll, Janet Pavese, Juan Chavez, James Bruce, Andrew Mazar, Antoinette Nibbs, Wayne Anderson, Lin Li, Borko Jovanovic, Sean Pruell, Matias Valsecchi, Giulio Francia, Rick Betori, Karl Scheidt, Raymond Bergan
Increased cancer cell motility constitutes a root cause of end organ destruction and mortality, but its complex regulation represents a barrier to precision targeting. We use the unique characteristics of small molecules to probe and selectively modulate cell motility. By coupling efficient chemical synthesis routes to multiple upfront in parallel phenotypic screens, we identify that KBU2046 inhibits cell motility and cell invasion in vitro. Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone destruction, and prolongs survival at nanomolar blood concentrations after oral administration...
June 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29934492/a-systems-biology-based-approach-to-uncovering-molecular-mechanisms-underlying-effects-of-traditional-chinese-medicine-qingdai-in-chronic-myelogenous-leukemia-involving-integration-of-network-pharmacology-and-molecular-docking-technology
#19
Chao Zhou, LiJuan Liu, Jing Zhuang, JunYu Wei, TingTing Zhang, ChunDi Gao, Cun Liu, HuaYao Li, HongZong Si, ChangGang Sun
BACKGROUND The method of multiple targets overall control is increasingly used to predict the main active ingredient and potential target group of Chinese traditional medicines and to determine the mechanisms involved in their curative effects. Qingdai is the main traditional Chinese medicine used in the treatment of chronic myelogenous leukemia (CML), but the complex active ingredients and antitumor targets in treatment of CML have not been clearly defined in previous studies. MATERIAL AND METHODS We constructed a protein-protein interaction network diagram of CML with 638 nodes (proteins) and 1830 edges, based on the biological function of chronic myelocytic leukemia by use of Cytoscape, and we determined 19 key gene nodes in the CML molecule by network topological properties analysis in a data bank...
June 23, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29934348/pharmacological-inhibition-of-erk-signaling-rescues-pathophysiology-and-behavioral-phenotype-associated-with-16p11-2-chromosomal-deletion-in-mice
#20
J Pucilowska, J Vithayathil, M Pagani, C Kelly, J C Karlo, C Robol, I Morella, A Gozzi, R Brambilla, G E Landreth
The human 16p11.2 microdeletion is one of the most common gene copy number variations linked to autism, but the pathophysiology associated with this chromosomal abnormality is largely unknown. The 593-kb deletion contains the ERK1 gene and other genes that converge onto the ERK/MAP kinase pathway. Perturbations in ERK signaling are linked to a group of related neurodevelopmental disorders hallmarked by intellectual disability, including autism. We report that mice harboring the 16p11.2 deletion exhibit a paradoxical elevation of ERK activity, cortical cytoarchitecture abnormalities and behavioral deficits...
June 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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