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Yu-Yan Li, Guang Zheng, Liang Liu
OBJECTIVE: To decipher the possible mechanisms of Sinomenium Acutum (SA) in treating diseases by a bioinformatics method. METHODS: SA ingredients were searched according to Chinese Pharmacopoeia, Chinese Medicine Dictionary and Traditional Chinese Medicines Database (TCMD). Active compounds and target proteins of SA were acquired through the Pubchem platform. Pathway, network and function analyses of SA were performed with ingenuity pathway analysis (IPA), a bioinformatics analysis platform...
March 21, 2018: Chinese Journal of Integrative Medicine
Norikazu Yabuta, Chie Ota, Towa Sasakura, Yoko Naito, Daisuke Okuzaki, Kohshiro Fukushima, Hiroshi Nojima
p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here that TAp63 phosphorylated at T46/T281 specifically upregulates the late cornified envelope 1C (LCE1C) gene that is essential at a relatively late stage of epithelial development. We identified these phosphorylation sites during a search for the targets of Cyclin G-associated kinase (GAK) in vitro...
March 20, 2018: Scientific Reports
Tanuj Sharma, Mohammad Imran Siddiqi
Unique intrinsic properties of peptides like low toxicity, high biological activity and specificity make them attractive therapeutic agents. PDZ binding peptide inhibitors have been demonstrated for curing of Alzheimer, Parkinson, Dementia and other central nervous system ailments. In this article, we report the successful use of an integrated computational protocol to analyze the structural basis of how peptides bind to the shallow groove of the third PDZ domain (PDZ3) from the Post Synaptic Density (PSD-95) protein...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Brandon K Martinez, C Michael White
OBJECTIVE: To review the role of inflammatory suppression in patients with atherosclerotic cardiovascular disease (ASCVD) with a focus on the interleukin-1β blocker canakinumab. DATA SOURCES: An Ovid MEDLINE literature search (1946 to February 2018) was performed using search terms inflammation, ASCVD, atherosclerosis, C-reactive protein, canakinumab. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the impact of pharmacological agents, including canakinumab, on inflammation as measured by high-sensitivity C-reactive protein (hsCRP) and the association with reducing ASCVD events were evaluated...
March 1, 2018: Annals of Pharmacotherapy
Winston X Yan, Shaorong Chong, Huaibin Zhang, Kira S Makarova, Eugene V Koonin, David R Cheng, David A Scott
Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c...
March 9, 2018: Molecular Cell
Karolin Eifler, Sabine A G Cuijpers, Edwin Willemstein, Jonne A Raaijmakers, Dris El Atmioui, Huib Ovaa, René H Medema, Alfred C O Vertegaal
Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798...
March 16, 2018: Nature Communications
Emanuele F Osimo, Rudolf N Cardinal, Peter B Jones, Golam M Khandaker
Low-grade inflammation is a risk factor for depression, psychosis and other major psychiatric disorders. It is associated with poor response to antidepressant and antipsychotics, and could potentially be a treatment target. However, there is limited data on the prevalence of low-grade inflammation in major psychiatric disorders, and on the characteristics of patients who show evidence of inflammation. We examined the prevalence of low-grade inflammation and associated socio-demographic and clinical factors in acute psychiatric inpatients...
March 1, 2018: Psychoneuroendocrinology
Sheikh Arslan Sehgal, Mirza A Hammad, Rana Adnan Tahir, Hafiza Nisha Akram, Faheem Ahmad
BACKGROUND: As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. OBJECTIVE: To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases...
March 15, 2018: Current Neuropharmacology
Albert J Czaja
Autoimmune hepatitis lacks a quantifiable biomarker that is close to its pathogenic mechanisms and that accurately reflects inflammatory activity, correlates with treatment response, and ensures inactive disease before treatment withdrawal. Areas covered: Micro-ribonucleic acids, programmed death-1 protein and its ligands, macrophage migration inhibitory factor, soluble CD163, B cell activating factor, and metabolite patterns in blood were considered the leading candidates as therapeutic biomarkers after search of PubMed from August 1981 to August 2017 using the search words "biomarkers of autoimmune hepatitis"...
March 14, 2018: Expert Review of Gastroenterology & Hepatology
Sneha Munshi, Soundhararajan Gopi, Sandhyaa Subramanian, Luis A Campos, Athi N Naganathan
The amplitude of thermodynamic fluctuations in biological macromolecules determines their conformational behavior, dimensions, nature of phase transitions and effectively their specificity and affinity, thus contributing to fine-tuned molecular recognition. Unique among large-scale conformational changes in proteins are temperature-induced collapse transitions in intrinsically disordered proteins (IDPs). Here, we show that CytR DNA-binding domain, an IDP that folds on binding DNA, undergoes a coil-to-globule transition with temperature in the absence of DNA while exhibiting energetically decoupled local and global structural rearrangements, and maximal thermodynamic fluctuations at the optimal bacterial growth temperature...
March 10, 2018: Nucleic Acids Research
Sandra Bien-Möller, Ellen Balz, Susann Herzog, Laura Plantera, Silke Vogelgesang, Kerstin Weitmann, Carolin Seifert, Matthias A Fink, Sascha Marx, Angela Bialke, Chitra Venugopal, Sheila K Singh, Wolfgang Hoffmann, Bernhard H Rauch, Henry W S Schroeder
Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed...
2018: Stem Cells International
Daniel J Rigden, Jens M H Thomas, Felix Simkovic, Adam Simpkin, Martyn D Winn, Olga Mayans, Ronan M Keegan
Molecular replacement (MR) is the predominant route to solution of the phase problem in macromolecular crystallography. Although routine in many cases, it becomes more effortful and often impossible when the available experimental structures typically used as search models are only distantly homologous to the target. Nevertheless, with current powerful MR software, relatively small core structures shared between the target and known structure, of 20-40% of the overall structure for example, can succeed as search models where they can be isolated...
March 1, 2018: Acta Crystallographica. Section D, Structural Biology
Rafat Ali, Shalini Singh, Wahajul Haq
BACKGROUND: Smac mimetics (also known as IAP antagonist) are a new class of targeted drugs having a goal to suppress the IAPs, reestablishing the apoptotic pathways and inducing cancer cell death. Therefore, development of Smac mimetics was consideredan attractive strategy for the development of new anticancer drugs. Lots of review has been come in yesteryears which mainly discussed about biology of IAPs and their role in cancer development. But none of these reviews focused on the chemical synthesis of Smac mimetics...
March 12, 2018: Current Medicinal Chemistry
Jessica M de Souza, Bruno D C Goncalves, Marcus V Gomez, Luciene B Vieira, Fabiola M Ribeiro
Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death...
2018: Frontiers in Pharmacology
W Masson, M Lobo, D Siniawski, M Huerín, G Molinero, R Valéro, J P Nogueira
BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors are a class of drugs that targets the CETP enzyme to significantly increase serum high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels. As HDL-C has potential antidiabetic properties, and the beneficial effects of CETP drugs on glucose homoeostasis have not been sufficiently studied, the aims of this study were: (1) to evaluate the effect of CETP inhibitors on the incidence of diabetes; and (2) to assess the association between CETP inhibitor-induced changes in HDL-C levels and incidence of diabetes...
February 20, 2018: Diabetes & Metabolism
William A Masters, Katherine L Rosettie, Sarah Kranz, Goodarz Danaei, Patrick Webb, Dariush Mozaffarian
Improving maternal and child nutrition in resource-poor settings requires effective use of limited resources, but priority-setting is constrained by limited information about program costs and impacts, especially for interventions designed to improve diet quality. This study utilized a mixed methods approach to identify, describe and estimate the potential costs and impacts on child dietary intake of 12 nutrition-sensitive programs in Ethiopia, Nigeria and India. These potential interventions included conditional livestock and cash transfers, media and education, complementary food processing and sales, household production and food pricing programs...
March 7, 2018: Health Policy and Planning
Jianqiang Miao, Xiuhuan Li, Dong Lin, Xili Liu, Brett M Tyler
Oxysterol-binding protein (OSBP) related proteins (ORPs) are a large conserved family of lipid transfer proteins in eukaryotes. In oomycetes, some ORPs are the target of the novel oomycide oxathiapiprolin. By searching the Phytophthora sojae genome database, two ORP proteins, PsORP1 (Protein ID: 558498) and PsORP2 (Protein ID: 470921), were found. Here we investigated the biological function of PsORP2. The expression level of PsORP2 was higher in germinated cysts and late infection than in other developmental stages...
March 9, 2018: Environmental Microbiology Reports
Xin Zhang, Tantan Gao, Qi Peng, Lai Song, Jie Zhang, Yunrong Chai, Dongmei Sun, Fuping Song
Bacillus thuringiensis bacteria show insecticidal activities that rely upon the production of insecticidal crystal proteins, which are encoded by cry or cyt genes and can target a variety of insect pests. It has been shown that cry1Ac is the only cry gene in B. thuringiensis subsp. kurstaki HD73 (B. thuringiensis HD73) and its expression is controlled by both σE and σK . Here, we report a novel σE -dependent strong promoter of a non-cry gene (HD73_5014), which can direct strong cry1Ac gene expression in B...
March 8, 2018: Applied Microbiology and Biotechnology
Shihua Zhang, Liang Zhang, Yijun Wang, Jian Yang, Mingzhi Liao, Shoudong Bi, Zhongwen Xie, Chi-Tang Ho, Xiaochun Wan
Tea is one of the most popular non-alcoholic beverages consumed worldwide. Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities. However, a complete interacting profile between tea bioactive compounds (TBCs) and their target genes is lacking, which put an obstacle in the study of healthy function of tea. To fill this gap, we developed a database of target genes of TBCs (TBC2target, based on a pharmacophore mapping approach...
2018: Frontiers in Plant Science
Harry D Dawson, Joan K Lunney
Pigs are a major source of food worldwide; preventing and treating their infectious diseases is essential, requiring a thorough understanding of porcine immunity. The use of pigs as models for human physiology is a growing area; progress in this area has been limited because the immune toolkit is not robust. The international community has established cluster of differentiation (CD) markers for assessing cells involved in immunity as well as characterizing numerous other cells like stem cells. Overall, for humans 419 proteins have been designated as CD markers, each reacting with a defined set of antibodies (Abs)...
February 22, 2018: Research in Veterinary Science
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