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https://www.readbyqxmd.com/read/29783183/identification-of-novel-phosphatidic-acid-binding-domain-on-sphingosine-kinase-1-of-arabidopsis-thaliana
#1
Shatakshi Pandit, Vikram Dalal, Girish Mishra
Phosphatidic acid (PA) is an important lipid signaling molecule which interacts with Arabidopsis thaliana Sphingosine kinase1 (AtSPHK1) during several abiotic stresses particularly drought stress as a result of Abscisic acid (ABA) signaling in guard cells. PA molecules respond by generating lipid signal and/or by binding and translocating target proteins to membrane. However, site of interaction and role of PA binding to AtSPHK1 is not clear yet. Owing to the importance of AtSPHK1 during stress signaling it is imperative to decipher the site of PA interaction with AtSPHK1...
May 8, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29783089/self-stabilized-silk-sericin-based-nanoparticles-in-vivo-biocompatibility-and-reduced-doxorubicin-induced-toxicity
#2
Doudou Hu, Ting Li, Zongpu Xu, Di Liu, Mingying Yang, Liangjun Zhu
A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, the discounted tumor targetability, delivery efficacy and possible side effects limit the application in the vascular delivery of NPs. Here we present the water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) could resist to the serum protein adsorption, preventing the formation of particle agglomerates...
May 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29783075/mir-19a-negatively-regulated-the-expression-of-pten-and-promoted-the-growth-of-ovarian-cancer-cells
#3
Yuhong Wang, Shuzhen Zhao, Lihong Zhu, Quanle Zhang, Yanfang Ren
Ovarian cancer is the most lethal malignancy of the women genital tract. Exploring novel factors involved in the development of ovarian cancer and characterizing the molecular mechanisms by which regulate the tumorigenesis of ovarian cancer are quite necessary. Here, we found that miR-19a was highly expressed in ovarian cancer tissues and cell lines. Overexpression of miR-19a promoted the viability of ovarian cancer cells, while down-regulation of miR-19a inhibited the growth of ovarian cancer cells. To further understand the underlying molecular mechanism of miR-19a in regulating ovarian cancer cell growth, the downstream targets of miR-19a were predicted...
May 18, 2018: Gene
https://www.readbyqxmd.com/read/29783070/cdh17-alters-mmp-2-expression-via-canonical-nf-%C3%AE%C2%BAb-signalling-in-human-gastric-cancer
#4
Xiao-Jie Jiang, Jing Lin, Qing-He Cai, Jian-Feng Zhao, Hui-Jiao Zhang
Gastric cancer (GC), one of the most common cancers of the digestive system, results in high morbidity and mortality, but the molecular mechanisms underlying GC remain largely unknown. Cadherin-17 (CDH17) is a nonclassical member of the cadherin (CDH) superfamily of calcium-dependent proteins. Despite recent advances in the understanding of CDH17 biology, the mechanism of CDH17 in GC proliferation, migration, and invasion has not been extensively studied. In the present study, we observed that CDH17 expression was increased in GC tissues compared with para-carcinoma tissues and was correlated with lymph node metastasis and the AJCC stage...
May 18, 2018: Gene
https://www.readbyqxmd.com/read/29783016/systematic-investigation-of-the-erigeron-breviscapus-mechanism-for-treating-cerebrovascular-disease
#5
Jiangmei Wang, Yangyang Chen, Baoshi Liu, Qian Wang, Lulu Zhang, Zhenzhong Wang, Jun Zhou, Wei Xiao, Chunli Zheng, Yonghua Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Cerebrovascular diseases (CBVDs), characterized by striking morbidity and mortality, have become the most common life-threatening diseases. The existing drugs of CBVDs target one or a few of pathogenic factors, the efficacy of which is limited because of the complexity of CBVDs. Traditional Chinese medicine (TCM), featured by multi-component and multi-target endows the great effectiveness in CBVDs treatment. For instance, Erigeron breviscapus (vant.) Hand...
May 18, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29782976/ldiscu-is-a-2fe-2s-scaffold-protein-which-interacts-with-ldiscs-and-its-expression-is-modulated-by-fe-s-proteins-in-leishmania-donovani
#6
Krishn Pratap Singh, Shadab Anwar, Amir Zaidi, Kuljit Singh, Pradeep Das, Samudrala Gourinath, Vahab Ali
The pathogenicity of protozoan parasites is frequently attributed to their ability to circumvent the deleterious effects of ROS and Fe-S clusters are among their susceptible targets with paramount importance for parasite survival. The biogenesis of Fe-S clusters is orchestrated by ISC system; the sulfur donor IscS and scaffold protein IscU being its core components. However, among protozoan parasites including Leishmania, no information is available regarding biochemical aspect of IscU, its interaction partners and regulation...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782974/molecular-therapy-using-sirna-recent-trends-and-advances-of-multi-target-inhibition-of-cancer-growth
#7
REVIEW
Shweta Jain, Kamla Pathak, Ankur Vaidya
RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782894/screening-of-the-mmv-and-gsk-open-access-chemical-boxes-using-a-viability-assay-developed-against-the-kinetoplastid-crithidia-fasciculata
#8
Wakisa Kipandula, Simon A Young, Stuart A MacNeill, Terry K Smith
Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes...
May 18, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29782863/analysis-of-mulberry-leaf-components-in-the-treatment-of-diabetes-using-network-pharmacology
#9
Qi Ge, Liang Chen, Min Tang, Shu Zhang, Lu Gao, Shangshang Ma, Lanlan Liu, Ming Kong, Qin Yao, Keping Chen, Fan Feng
Mulberry leaves are one of the most commonly used medicinal and herbaceous traditional Chinese medicines that are currently considered for the treatment of diabetes mellitus and its complications. The alkaloids, flavonoids, and polysaccharides in mulberry leaves impart regulatory effects on blood sugar levels. To identify the hypoglycemia-related active components in mulberry leaves and their targets, the present study conducted gas chromatography-mass spectrometer (GC/MS), which identified 202 components of mulberry leaf, of which 22 components may have significant curative effects on diabetes mellitus and its complications and chronic inflammation...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782858/the-antidepressant-effects-of-%C3%A9-tocopherol-are-related-to-activation-of-autophagy-via-the-ampk-mtor-pathway
#10
Xiaoyan Huang, Haoran Wu, Ruizhi Jiang, Guangda Sun, Jiali Shen, Mengling Ma, Chuanhui Ma, Shijia Zhang, Zhiheng Huang, Qinan Wu, Gang Chen, Weiwei Tao
The purpose of the present study was to investigate whether ɑ-tocopherol exhibited neuro-protective effects in chronic unpredictable mild stress (CUMS) mice through the regulation of autophagy. Deficits in behavioural tests, including a sucrose preference test, open field test, forced swim test, and tail suspension test, were ameliorated following ɑ-tocopherol administration. To study the potential mechanism, western blots were performed on both prefrontal cortex and hippocampus samples. Similar to the degree of autophagy, the activities of adenosine monophosphate-activated protein kinase (AMPK) and Unci-51 like autophagy activating kinase-1 (ULK1) were decreased after CUMS stimulation...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782856/sirt1-activation-prevents-anti-thy-1-1-mesangial-proliferative-glomerulonephritis-in-the-rat-through-the-nrf2-are-pathway
#11
Kaipeng Huang, Ruiming Li, Wentao Wei
Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/ anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782854/combined-treatment-with-sorafenib-and-silibinin-synergistically-targets-both-hcc-cells-and-cancer-stem-cells-by-enhanced-inhibition-of-the-phosphorylation-of-stat3-erk-akt
#12
Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782850/histone-deacetylase-1-promotes-glioblastoma-cell-proliferation-and-invasion-via-activation-of-pi3k-akt-and-mek-erk-signaling-pathways
#13
Shun Li, Xiangrong Chen, Lifang Mao, Kashif Rafiq Zahid, Jun Wen, Liu Zhang, Maoying Zhang, Junwei Duan, Jie Duan, Xiaohong Yin, Yuanchuan Wang, Long Zhao, Xiaoping Tang, Xiangyu Wang, Guozheng Xu
Histone deacetylase 1 (HDAC1) plays a crucial role in cancer progression and development. This enzyme has been confirmed to be a key regulator of tumor biology functions, such as tumor cell proliferation, migration and invasion. However, HDAC1 expression in glioma remains controversial, and its specific function and molecular mechanism in glioblastoma is poorly understood. In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively...
May 18, 2018: Brain Research
https://www.readbyqxmd.com/read/29782836/dancing-with-the-diva-hsp90-client-interactions
#14
REVIEW
Martina Radli, Stefan G D Rüdiger
The molecular chaperone Hsp90 is involved in the folding, maturation and degradation of a large number structurally and sequentially unrelated clients, often connected to serious diseases. Elucidating the principles of how Hsp90 recognises this large variety of substrates is essential for comprehending the mechanism of this chaperone machinery, as well as it is a prerequisite for the design of client specific drugs targeting Hsp90. Here, we discuss the recent progress in understanding the substrate recognition principles of Hsp90 and its implications for the role of Hsp90 in the lifecycle of (signalling) molecules...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#15
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782699/endoplasmic-reticulum-targeted-fluorescent-nanodot-with-large-stokes-shift-for-vesicular-transport-monitoring-and-long-term-bioimaging
#16
Leilei Shi, Xihui Gao, Wangzhang Yuan, Li Xu, Hongping Deng, Chenwei Wu, Jiapei Yang, Xin Jin, Chuan Zhang, Xinyuan Zhu
Herein, a highly stable aggregation-induced emission (AIE) fluorescent nanodot assembled by an amphiphilic quinoxalinone derivative-peptide conjugate, namely Quino-1-Fmoc-RACR (also termed as Q1-PEP), which exhibits large Stokes shift and an endoplasmic reticulum (ER)-targeting capacity for bioimaging is reported. It is found that the resulting nanodot can effectively enter the ER with high fluorescent emission. As the ER is mainly involved in the transport of synthesized proteins in vesicles to the Golgi or lysosomes, the Q1-PEP nanodot with ER-targeting capacity can be used to monitor vesicular transport inside the cells...
May 21, 2018: Small
https://www.readbyqxmd.com/read/29782552/role-of-kinesins-in-directed-adenovirus-transport-and-cytoplasmic-exploration
#17
Jie Zhou, Julian Scherer, Julie Yi, Richard B Vallee
Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#18
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782529/molecular-effect-of-an-optn-common-variant-associated-to-paget-s-disease-of-bone
#19
Iris A L Silva, Natércia Conceição, Édith Gagnon, Jacques P Brown, M Leonor Cancela, Laëtitia Michou
Paget's disease of bone (PDB) is a chronic bone disorder and although genetic factors appear to play an important role in its pathogenesis, to date PDB causing mutations were identified only in the Sequestosome 1 (SQSTM1) gene at the PDB3 locus. PDB6 locus, also previously linked to PDB, contains several candidate genes for metabolic bone diseases. We focused our analysis in the most significantly associated variant with PDB, within the Optineurin (OPTN) gene, i.e. the common variant rs1561570. Although it was previously shown to be strongly associated with PDB in several populations, its contribution to PDB pathogenesis remains unclear...
2018: PloS One
https://www.readbyqxmd.com/read/29782496/development-of-a-toolkit-for-piggybac-mediated-integrative-transfection-of-the-human-filarial-parasite-brugia-malayi
#20
Canhui Liu, Amruta S Mhashilkar, Johan Chabanon, Shulin Xu, Sara Lustigman, John H Adams, Thomas R Unnasch
BACKGROUND: The human filarial parasites cause diseases that are among the most important causes of morbidity in the developing world. The elimination programs targeting these infections rely on a limited number of drugs, making the identification of new chemotherapeutic agents a high priority. The study of these parasites has lagged due to the lack of reverse genetic methods. METHODOLOGY/PRINCIPAL FINDINGS: We report a novel co-culture method that results in developmentally competent infective larvae of one of the human filarial parasites (Brugia malayi) and describe a method to efficiently transfect the larval stages of this parasite...
May 21, 2018: PLoS Neglected Tropical Diseases
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