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Membrane potentional

Keyu Li, Jiabei Wang, Jihua Han, Yaliang Lan, Changming Xie, Shangha Pan, Lianxin Liu
BACKGROUND: NET (NocA/Nlz, Elbow, Tlp-1) family members have recently emerged as important players in the development of human cancers. Zinc finger protein 703 (ZNF703), locating on chromosome 8 (8p11.23), a member of the NET/Nlz family of zinc finger transcription factors, had been demonstrated to be a much novel oncogene of several malignancies. This study aimed to investigate the expression of ZNF703 in cholangiocarcinoma (CCA) and attempted to elucidate its biological effects in CCA progression...
October 13, 2016: Oncotarget
Michael S Zhang, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with well characterized anti-microbial properties. Because of these properties, GML is widely used in food, cosmetics, and personal care products and currently being tested as a therapeutic for menstrual associated toxic shock syndrome, superficial wound infections, and HIV transmission. Recently, we have described that GML potently suppresses select T cell receptor (TCR)-induced signaling events, leading to reduced human T cell effector functions. However, how soluble host factors present in the blood and at sites of infection affect GML-mediated human T cell suppression is unknown...
2016: PloS One
Kunihiko Watanabe
It is becoming well-known that bacterial cells produce membrane vesicles (MVs) from the cell surface in a budding manner, whereas the detailed mechanisms of MV biogenesis remain unclear. MVs are not authentic cells, since they are observed to be between 20 and 300 nm in size but have a structure close to the subcellular compartments. In a sense, the structure of MVs containing biogenic and cellular substances and their behavior look similar to those of viruses. Due to these scientific facts, several potent applications employing MVs as a promising tool have been proposed and reported...
October 19, 2016: Applied Microbiology and Biotechnology
Shekhar Dethe, M Deepak, Amit Agarwal
BACKGROUND: Bacopa monnieri (L.) Wettst., commonly known as Brahmi, is renowned in Indian traditional system for its potent memory enhancing activity, which has been validated by various scientific studies. OBJECTIVE: The objective of this study was to understand the molecular mechanism of memory enhancing activity of BacoMind(®) (BM), a standardized extract of B. monnieri. MATERIALS AND METHODS: BM was screened in vitro in a panel of cell-free and receptor-transfected cell assays...
July 2016: Pharmacognosy Magazine
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Aritreyee Datta, Vikas Yadav, Anirban Ghosh, Jaesun Choi, Dipita Bhattacharyya, Rajiv K Kar, Humaira Ilyas, Arkajyoti Dutta, Eunseol An, Jayanta Mukhopadhyay, Dongkuk Lee, Kaustuv Sanyal, Ayyalusamy Ramamoorthy, Anirban Bhunia
There is a significant need for developing compounds that kill Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis in immunocompromised individuals. Here, we report the mode of action of a designed antifungal peptide, VG16KRKP (VARGWKRKCPLFGKGG) against C. neoformans. It is shown that VG16KRKP kills fungal cells mainly through membrane compromise leading to efflux of ions and cell metabolites. Intracellular localization, inhibition of in vitro transcription, and DNA binding suggest a secondary mode of action for the peptide, hinting at possible intracellular targets...
October 18, 2016: Biophysical Journal
R Lin, Q Wang, B Qi, Y Huang, G Yang
Neuromedin S (NMS), a 36-amino acid neuropeptide, has been found to be involved in the regulation of the endocrine activity. It has been also detected in immune tissues in mammals, what suggests that NMS may play an important role in the regulation of immune response. The aim of this study was to demonstrate the presence of NMS receptor 1 (NMU1R) and effect of NMS in pig splenic lymphocytes (SPLs) and pulmonary alveolar macrophages (PAMs). The presence of NMU1R in pig SPLs and PAMs was respectively confirmed by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunocytochemical methods...
September 1, 2016: Polish Journal of Veterinary Sciences
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
Yoo Jeong Kim, Hyejin Jeon, Seok Hyeon Na, Hyo Il Kwon, Gati Noble Selasi, Asiimwe Nicholas, Tae In Park, Sang Hwa Lee, Je Chul Lee
Stenotrophomonas maltophilia has become one of the most prevalent opportunistic pathogens in hospitalized patients. This microorganism secretes outer membrane vesicles (OMVs), but the pathogenesis of S. maltophilia as it relates to OMVs has not been characterized. This study investigated the cytotoxic activity of S. maltophilia OMVs and their ability to induce inflammatory responses both in vitro and in vivo S. maltophilia ATCC 13637 and two clinical isolates were found to secrete spherical OMVs during in vitro culture...
October 17, 2016: Pathogens and Disease
Maddison Turner, Larissa Reid, Mercedes Munkonda, Dylan Burger
OBJECTIVE: Diabetes and hypertension are cognate diseases that often coexist, potentiating one's risk for cardiovascular complications. Both diseases are typified by the development of endothelial dysfunction and are accompanied by increased circulating endothelial microparticles (eMPs). Microparticles are small membrane-derived vesicles that are secreted ubiquitously following cell stress. We have previously shown that eMPs are sensitive markers of vascular injury in hypertension and identified eMP-mediated signaling pathways that lead to endothelial injury...
September 2016: Journal of Hypertension
Jinshan Jin, Ying-Hsin Hsieh, Jianmei Cui, Krishna Damera, Chaofeng Dai, Arpana S Chaudhary, Hao Zhang, Hsiuchin Yang, Nannan Cao, Chun Jiang, Martti Vaara, Binghe Wang, Phang C Tai
With the widespread emergence of drug resistance, there is an urgent need to search for new antimicrobials, especially those against Gram-negative bacteria. Along this line, the identification of viable targets is a critical first step. The protein translocase SecA is commonly believed to be an excellent target for the development of broad-spectrum antimicrobials. In recent years, we developed three structural classes of SecA inhibitors that have proven to be very effective against Gram-positive bacteria. However, we have not achieved the same level of success against Gram-negative bacteria, despite the potent inhibition of SecA in enzyme assays by the same inhibitors...
October 18, 2016: ChemMedChem
Eun Young Park, Joo-Il Kim, Dong-Gyu Leem, Ji-Sun Shin, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Jung-Hye Choi, Yong Sup Lee, Kyung-Tae Lee
Previously, we reported that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ), a synthetic analogue of resveratrol had anti-inflammatory and G2/M cell cycle arrest activities, but the underlying molecular mechanism of cytotoxic effects of this compound was not determined. In this study, 8-ADEQ displayed potent cytotoxicity and triggered apoptosis in HL-60 cells as evidenced by DNA fragmentation, DNA ladder formation, and the externalization of Annexin V-targeted phosphatidylserine residues in HL-60 cells...
October 13, 2016: Oncology Reports
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
Denise Hübner, Milena R Kaluđerović, Santiago Gómez-Ruiz, Goran N Kaluđerović
Two ionic triphenyltin(IV) chloride carboxylato compounds of the formula [NHEt3 ][Ph3 SnCl(L)] (LH = N-phthaloylglycine (P-GlyH), 1; 1,2,4-benzenetricarboxylic 1,2-anhydride (BTCH), 2) were tested for the in vitro activity against 518A2 (melanoma), FaDu (head and neck carcinoma), HT-29 (colon cancer), MCF-7 (breast carcinoma) and SW1736 (thyroid cancer) cell lines. The ammonium salts of carboxylic acids are found to be not active, while anionic [Ph3 SnCl(L)](-) exhibited high cytotoxicity in nM range, higher both activity and selectivity than cisplatin...
October 17, 2016: Chemical Biology & Drug Design
Keisuke Kaneko, Yuko Koyanagi, Yoshiyuki Oi, Masayuki Kobayashi
Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates Ih, K(+), and voltage-gated Na(+) currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation...
October 13, 2016: Neuroscience
Eric Murillo-Rodríguez, Sergio Machado, Nuno Barbosa Rocha, Henning Budde, Ti-Fei Yuan, Oscar Arias-Carrión
The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents...
October 13, 2016: Neuroscience
Michela De Bellis, Roberta Carbonara, Julien Roussel, Alessandro Farinato, Ada Massari, Sabata Pierno, Marilena Muraglia, Filomena Corbo, Carlo Franchini, Maria Rosaria Carratù, Annamaria De Luca, Diana Conte Camerino, Jean-François Desaphy
Although the sodium channel blocker, mexiletine, is the first choice drug in myotonia, some myotonic patients remain unsatisfied due to contraindications, lack of tolerability, or incomplete response. More therapeutic options are thus needed for myotonic patients, which require clinical trials based on solid preclinical data. In previous structure-activity relationship studies, we identified two newly-synthesized derivatives of tocainide, To040 and To042, with greatly enhanced potency and use-dependent behavior in inhibiting sodium currents in frog skeletal muscle fibers...
October 12, 2016: Neuropharmacology
Derell Hardman, Daniel McFalls, Stylianos Fakas
Phosphatidic acid phosphatase (PAP) catalyzes the committed step of triacylglycerol (TAG) biosynthesis and thus regulates the amounts of TAG produced by the cell. TAG is the target of biotechnological processes developed for the production of food lipids or biofuels. These processes are using oleaginous microorganisms like the yeast Yarrowia lipolytica as the TAG producers. Thus manipulating key enzymatic activities like PAP in Y. lipolytica could drive lipid biosynthesis towards TAG production and increase TAG yields...
October 15, 2016: Yeast
Takuya Kaji, Motoki Murai, Hiroaki Itoh, Jyunichiro Yasukawa, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue
Lysocin E (1) is a structurally complex 37-membered depsipeptide comprising 12 amino-acid residues with an N-methylated amide and an ester linkage. Compound 1 binds to menaquinone (MK) in the bacterial membrane to exert its potent bactericidal activity. To decipher the biologically important functionalities within this unique antibiotic, we performed a comprehensive structure-activity relationship (SAR) study by systematically changing the side-chain structures of l-Thr-1, d-Arg-2, N-Me-d-Phe-5, d-Arg-7, l-Glu-8, and d-Trp-10...
October 14, 2016: Chemistry: a European Journal
Brian Murray, C Seth Pearson, Alexa Aranjo, Dinesh Cherupalla, Georges Belfort
As pathogenic bacteria become resistant to traditional antibiotics, alternate approaches such as designing and testing new potent selective antimicrobial peptides (AMP) are increasingly attractive. However, while much is known regarding the relationship between AMP sequence and potency, less research has focused on developing links between AMP properties, such as design and structure, with mechanism. Here we use four natural AMPs of varying known secondary structures and mechanisms of lipid bilayer disruption as controls to determine the mechanisms of four rationally designed AMPs with similar secondary structures and rearranged amino acid sequences...
October 13, 2016: Journal of Biological Chemistry
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