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Membrane potentional

Younho Choi, James W Bowman, Jae U Jung
Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes...
March 19, 2018: Nature Reviews. Microbiology
Kelly M Storek, Marcy R Auerbach, Handuo Shi, Natalie K Garcia, Dawei Sun, Nicholas N Nickerson, Rajesh Vij, Zhonghua Lin, Nancy Chiang, Kellen Schneider, Aaron T Wecksler, Elizabeth Skippington, Gerald Nakamura, Dhaya Seshasayee, James T Koerber, Jian Payandeh, Peter A Smith, Steven T Rutherford
The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize a monoclonal antibody that selectively inhibits an essential component of the Escherichia coli β-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Michel Lagarde, Michel Guichardant, Nathalie Bernoud-Hubac, Catherine Calzada, Evelyne Véricel
The oxygenation metabolism of arachidonic acid (ArA) has been early described in blood platelets, in particular with its conversion into the potent labile thromboxane A2 that induces platelet aggregation and vascular smooth muscle cells contraction. In addition, the primary prostaglandins D2 and E2 have been mainly reported as inhibitors of platelet function. The platelet 12-lipoxygenase (12-LOX) product, i.e. the hydroperoxide 12-HpETE, appears to stimulate platelet ArA metabolism at the level of its release from membrane phospholipids through phospholipase A2 (cPLA2 ) and cyclooxygenase (COX-1) activities, the first enzymes in prostanoid production cascade...
March 16, 2018: Biochimica et Biophysica Acta
Fang Dai, Cui-Hong Yuan, Yuan Ji, Yu-Ting Du, Xia-Zhen Bao, Ling-Xi Wu, Xiao-Ling Jin, Bo Zhou
Altered redox status including higher levels of copper in cancer cells than in normal cells inspired many researchers to develop copper ionophores targeting this status. We have recently found that flavon-3-ol (3-HF) works as a potent Cu(II) ionophore by virtue of its keto-enol moiety. To further emphasize the significance of this moiety for developing Cu(II) ionophores, we herein designed a β-diketo analog of piperlongumine, PL-I, characterized by the presence of high proportion of the keto-enol form in dimethylsulfoxide and chloroform, and identified its keto-enol structure by NMR and theoretical calculations...
March 16, 2018: Free Radical Biology & Medicine
Shahbaz Ahmad Zakki, Zheng-Guo Cui, Lu Sun, Qian-Wen Feng, Meng-Ling Li, Hidekuni Inadera
BACKGROUND/AIMS: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. METHODS: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air...
March 15, 2018: Cellular Physiology and Biochemistry
Tomislav Rončević, Damir Vukičević, Nada Ilić, Lucija Krce, Goran Gajski, Marija Tonkić, Ivana Goić-Barišić, Larisa Zoranić, Yogesh Sonavane, Monica Benincasa, Davor Juretić, Ana Maravić, Alessandro Tossi
Antimicrobial peptides often show broad-spectrum activity due to a mechanism based on bacterial membrane disruption, which also reduces development of permanent resistance, a desirable characteristic in view of the escalating multidrug resistance problem. Host cell toxicity however requires design of artificial variants of natural AMPs to increase selectivity and reduce side effects. Kiadins were designed using rules obtained from natural peptides active against E. coli and a validated computational algorithm based on a training set of such peptides, followed by rational conformational alterations...
March 19, 2018: Journal of Medicinal Chemistry
Chengfei Hao, Xibo Zhang, Hongtao Zhang, Haitao Shang, Jianheng Bao, Haibo Wang, Zhonglian Li
PURPOSE: Plants produce a diversity of molecular scaffolds with tremendous pharmacological potential. In the present study we evaluated the anticancer activity of the plant-derived natural product sugiol. We also evaluated its effects on apoptosis-related key proteins, cell cycle phase distribution, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). METHODS: Cell viability was evaluated by MTT assay while clonogenic assay was done to determine the effects of sugiol on the cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
JinYing Liu, Xiaokang Liu, Wei Ma, Wei Kou, CaiLi Li, Jin Zhao
PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Chen Xiong, Yan-Zhao Wu, Yu Zhang, Zi-Xiao Wu, Xue-Yan Chen, Ping Jiang, Hui-Cai Guo, Ke-Rang Xie, Ke-Xin Wang, Su-Wen Su
Doxorubicin (DOX) is a potent and broad-spectrum anthracycline chemotherapeutic agent, but dose-dependent cardiotoxic side effects limit its clinical application. This toxicity is closely associated with the generation of reactive oxygen species (ROS) radical during DOX metabolism. The present study investigated the effects of Berberine (Ber) on DOX-induced acute cardiac injury in a rat model and analysed its mechanism in cardiomyocytes in vitro . Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and malondialdehyde (MDA) levels were significantly increased in the DOX group compared with the control group...
April 2018: Oncology Letters
Yan He, Kun Jia, Lei Li, Qi Wang, Shuhui Zhang, Jiaming Du, Heng Du
Mitochondrial dysfunction is a featured pathology underlying synaptic injury and neuronal stress in Alzheimer's disease (AD). In recent years, the vicious cycle between mitochondrial deficits and intra-neuronal Redox state imbalance has received considerable attention. In this regard, it is of great interest to determine whether antioxidants could alleviate mitochondrial dysfunction in AD-related conditions. Salvianolic acid B (SalB), a bioactive component of alvia miltiorrhiza Bge, is a potent antioxidant...
March 15, 2018: Biochemical and Biophysical Research Communications
Siew Mei Samantha Ng, Jia Mao Yap, Qiu Ying Lau, Fui Mee Ng, Esther Hong Qian Ong, Timothy Barkham, Jeanette Woon Pei Teo, Mohammad Alfatah, Kiat Whye Kong, Shawn Hoon, Prakash Arumugam, Jeffrey Hill, Cheng San Brian Chia
Vulvovaginal candidiasis (VVC) is a genital fungal infection afflicting approximately 75% of women globally and is primarily caused by the yeast Candida albicans. The extensive use of fluconazole, the first-line antifungal drug of choice, has led to the emergence of fluconazole-resistant C. albicans, creating a global clinical concern. This, coupled to the lack of new antifungal drugs entering the market over the past decade, has made it imperative for the introduction of new antifungal drug classes. Peptides with antifungal properties are deemed potential drug candidates due to their rapid membrane-disrupting mechanism of action...
March 9, 2018: European Journal of Medicinal Chemistry
Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
Ekaterina M Savelieva, Vladimir E Oslovsky, Dmitry S Karlov, Nikolay N Kurochkin, Irina A Getman, Sergey N Lomin, Georgy V Sidorov, Sergey N Mikhailov, Dmitry I Osolodkin, Georgy A Romanov
Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N6 -benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis...
March 12, 2018: Phytochemistry
Marta Martínez-Calle, Bárbara Olmeda, Paul Dietl, Manfred Frick, Jesús Pérez-Gil
The release of pulmonary surfactant by alveolar type II (ATII) cells is essential for lowering surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to alveolar collapse. Hydrophobic surfactant protein (SP)-B ensures the proper packing of newly synthesized surfactant particles, promotes the formation of the surface active film at the alveolar air-liquid interface and maintains its proper structure along the respiratory dynamics. We report that membrane-associated SP-B efficiently induces secretion of pulmonary surfactant by ATII cells, at the same level as potent secretagogues such as ATP...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Respati W Ranakusuma, Yupitri Pitoyo, Eka D Safitri, Sarah Thorning, Elaine M Beller, Sudigdo Sastroasmoro, Chris B Del Mar
BACKGROUND: Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics...
March 15, 2018: Cochrane Database of Systematic Reviews
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
Daniel Alejandro Peñalva, Silvia Antollini, Ernesto Ambroggio, Marta I Aveldaño, Maria Laura Fanani
In rat sperm head, sphingomyelin (SM) species that contain very long chain PUFA (V-SM) become ceramides (V-Cer) after inducing in vitro the acrosomal reaction. The reason for such a specific location of this conversion, catalysed by a sphingomyelinase (SMase), has received little investigation so far. Here, the effects of SMase were compared in unilamellar vesicles (LUVs, GUVs) containing phosphatidylcholine and either V-SM or a palmitate-rich SM (P-SM). In uniformly sized LUVs at 37 °C, more V-Cer was generated, and more rapidly, than P-Cer...
March 15, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Mouadh Mihoub, André Pichette, Balla Sylla, Charles Gauthier, Jean Legault
Betulin has a wide range of biological and pharmacological properties with its anticancer activity attracting most of the attention as it offers a possible alternative treatment to chemotherapy. However, betulin's in vivo biological effectiveness is limited by its poor solubility. As such, we synthesized polar glycosylated derivatives to increase its hydrosolubility and enhance its pharmacological properties. Among these synthesized compounds, 28-O-α-l-rhamnopyranosylbetulin 3β-O-α-l-rhamnopyranoside (Bi-L-RhamBet) was assessed for its cytotoxic effects against a suite of lung cancer cell lines...
2018: PloS One
Jing Zhang, Huihui Wu, Dan Jiang, Yongan Yang, Wenjian Tang, Kehan Xu
To identify the natural antifungal agents, the antifungal activities of Melaleuca leucadendra (L.) L. essential oil (ML-EO) from Fujian Province of China were assayed. Treatment of ML-EO in combination with the front-line using antibiotics against Candida led to synergistic effects. Electron microscopy analysis on the oil treated C. albicans cells revealed the formation of mesosome-like structures, suggesting well the membrane damage caused by the essential oil. The Griess assay by monitoring NO production in LPS-stimulated RAW264...
March 14, 2018: Natural Product Research
Amy N Jacobson, Biswa P Choudhury, Michael A Fischbach
Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides , makes up around 50% of the cells in a typical Western gut; these cells harbor ~300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants...
March 13, 2018: MBio
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