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https://www.readbyqxmd.com/read/28735047/sesamol-exhibits-potent-antimycobacterial-activity-underlying-mechanisms-and-impact-on-virulence-traits
#1
Sandeep Hans, Sharda Sharma, Saif Hameed, Zeeshan Fatima
OBJECTIVES: Novel strategies to overcome multidrug resistance (MDR) in Tuberculosis (TB) still remain a concern. Usage of natural compounds nowadays to surmount the increasing burden of MDR-TB has shown promising results. The aim of this study was to evaluate the antimycobacterial potential of sesamol (Ses) a natural phenolic compound against Mycobacterium smegmatis, a surrogate for MTB and its underlying mechanism of action along with its effect on mycobacterial virulence traits. METHODS: Cell surface phenotypes were estimated microscopically and spectrophotometrically respectively...
July 19, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28734478/ph-dependent-membrane-interactions-of-the-histidine-rich-cell-penetrating-peptide-lah4-l1
#2
Justine Wolf, Christopher Aisenbrey, Nicole Harmouche, Jesus Raya, Philippe Bertani, Natalia Voievoda, Regine Süss, Burkhard Bechinger
The histidine-rich designer peptide LAH4-L1 exhibits antimicrobial and potent cell-penetrating activities for a wide variety of cargo including nucleic acids, polypeptides, adeno-associated viruses, and nanodots. The non-covalent complexes formed between the peptide and cargo enter the cell via an endosomal pathway where the pH changes from neutral to acidic. Here, we investigated the membrane interactions of the peptide with phospholipid bilayers and its membrane topology using static solid-state NMR spectroscopy...
July 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28734085/novel-menadione-hybrids-synthesis-anticancer-activity-and-cell-based-studies
#3
Chakka Vara Prasad, Vadithe Lakshma Nayak, Sistla Ramakrishna, Uppuluri Venkata Mallavadhani
A series of novel menadione based triazole hybrids were designed and synthesized by employing copper catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data ((1) H NMR, (13) C NMR, IR and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7) and mouse melanoma (B-16) by using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity...
July 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28733553/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#4
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733229/estrogen-signaling-through-both-membrane-and-nuclear-receptors-in-the-liver-of-fathead-minnow
#5
Natàlia Garcia-Reyero, B Sumith Jayasinghe, Kevin J Kroll, Tara Sabo-Attwood, Nancy D Denslow
Estradiol is a potent sex steroid hormone that controls reproduction and other cellular pathways in fish. It is known to regulate important proteins such as vitellogenin, the egg yolk precursor protein, and zona radiata proteins that form the eggshell for fish eggs. These proteins are made in the liver and transported out into the blood from where they are taken up into the ovary during oogenesis. Estradiol can exert its influence directly through soluble nuclear receptors (there are three in fish) or indirectly through membrane receptors and a phosphorylation cascade...
July 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28731688/the-%C3%AF-configuration-of-the-www-motif-of-a-short-trp-rich-peptide-is-critical-for-targeting-bacterial-membranes-disrupting-preformed-biofilms-and-killing-methicillin-resistant-staphylococcus-aureus
#6
D Zarena, Biswajit Mishra, Tamara Lushnikova, Fangyu Wang, Guangshun Wang
Tryptophan-rich peptides, being short and suitable for large-scale chemical synthesis, are attractive candidates for developing a new generation of antimicrobials to combat antibiotic-resistant bacteria (superbugs). Although there are numerous pictures for membrane-bound structure of a single tryptophan (W), how multiple Trp amino acids assemble themselves and interact with bacterial membranes are poorly understood. This communication presents the three-dimensional structure for an eight-residue Trp-rich peptide (WWWLRKIW-NH2 with 50% W) determined by the improved 2D NMR method, which includes the measurements of 13C and 15N chemical shifts at natural abundance...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28730515/selective-induction-of-dna-damage-g2-abrogation-and-mitochondrial-apoptosis-by-leaf-extract-of-traditional-medicinal-plant-wrightia-arborea-in-k562-cells
#7
T Lakshmipriya, T Soumya, P R Jayasree, P R Manish Kumar
Plants have proved to be an important source of anti-cancer drugs. Wrightia arborea, an Indian Ayurvedic medicinal plant, is used traditionally to treat a variety of ailments. This study evaluates the antiproliferative/apoptotic potential of Wrightia arborea leaf extracts, prepared in different organic solvents, on cancer cell lines. MTT assay, light and fluorescence microscopy, flow cytometry, DNA laddering, alkaline comet assay, and western blotting were some of the techniques used for evaluation. Combinations of camptothecin, either with CHK1 inhibitor-PD407824 or with W...
July 20, 2017: Protoplasma
https://www.readbyqxmd.com/read/28728104/design-synthesis-and-evaluation-of-coumarin-pargyline-hybrids-as-novel-dual-inhibitors-of-monoamine-oxidases-and-amyloid-%C3%AE-aggregation-for-the-treatment-of-alzheimer-s-disease
#8
Hua-Li Yang, Pei Cai, Qiao-Hong Liu, Xue-Lian Yang, Fan Li, Jin Wang, Jia-Jia Wu, Xiao-Bing Wang, Ling-Yi Kong
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test...
July 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727445/an-antibiotic-that-inhibits-the-atpase-activity-of-an-abc-transporter-by-binding-to-a-remote-extracellular-site
#9
Leigh Morgan Matano, Heidi Gabrielle Morris, Anthony R Hesser, Sara E S Martin, Wonsik Lee, Tristan W Owens, Emaline Laney, Hidemasa Nakaminami, David Hooper, Timothy C Meredith, Suzanne Walker
Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics to treat resistant infections. In a high throughput screen (HTS) of 230,000 small molecules designed to identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into a small panel of potent compounds. We showed that these compounds target TarG, the transmembrane component of the two-component ATP-binding cassette (ABC) transporter TarGH, which exports WTA precursors to the cell surface for attachment to peptidoglycan...
July 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28726778/protection-of-mcc950-against-high-glucose-induced-human-retinal-endothelial-cell-dysfunction
#10
Yi Zhang, Xuehua Lv, Zizhong Hu, Xiaojian Ye, Xinhua Zheng, Yuzhi Ding, Ping Xie, Qinghuai Liu
Diabetic retinopathy (DR) is a well-known microvascular complication related to inflammation. Mcc950 is a potent and specific inhibitor of the NLRP3 inflammasome but its influence on DR has not been studied. Thus, we evaluated the anti-inflammatory effects of Mcc950 on high-glucose-induced human retinal endothelial cells (HRECs) and the potential underlying mechanism. In surgical excised proliferative membranes from DR patients, high expression of NLRP3, caspase 1 and IL-1β was observed and co-localization of NLRP3 and IL-1β occurred in CD31+ labeled HRECs...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726636/live-cell-visualization-of-gasdermin-d-driven-pyroptotic-cell-death
#11
Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott
Pyroptosis is a form of cell death important in defenses against pathogens, but which can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, gasdermin D (GSDMD), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726635/as-cath1-6-novel-cathelicidins-with-potent-antimicrobial-and-immunomodulatory-properties-from-alligator-sinensis-play-pivotal-roles-in-host-anti-microbial-immune-responses
#12
Yan Chen, Shasha Cai, Xue Qiao, Mali Wu, Zhilai Guo, Renping Wang, Yi-Qun Kuang, Haining Yu, Yipeng Wang
Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of crocodilian immune system has remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1~6) were identified and characterized from the endangered Chinese Alligator ( Alligator sinensis )...
July 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28724841/sphingosine-1-phosphate-and-atherosclerosis
#13
Makoto Kurano, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28723974/alginate-hydrogels-allow-for-bioactive-and-sustained-release-of-vegf-c-and-vegf-d-for-lymphangiogenic-therapeutic-applications
#14
Kevin T Campbell, Dustin J Hadley, David L Kukis, Eduardo A Silva
Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications...
2017: PloS One
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#15
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#16
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28720131/anti-arthritic-activity-of-aqueous-methanolic-extract-and-various-fractions-of-berberis-orthobotrys-bien-ex-aitch
#17
Alamgeer, Ambreen Malik Uttra, Umme Habiba Hasan
BACKGROUND: The roots and stem bark of Berberis orthobotrys (Berberidaceae) have long been used traditionally to treat joint pain. Though, it has not been pharmacologically assessed for rheumatoid arthritis. The current study explores anti-arthritic activity and phytochemical analysis of aqueous-methanolic extract (30:70) and fractions (ethyl acetate, n-butanol, and aqueous) of Berberis orthobotrys roots. METHODS: Anti-arthritic potential was evaluated in vitro using protein denaturation (bovine serum albumin and egg albumin) and membrane stabilization methods at 12...
July 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28716495/3-5-bis-3-dimethylaminomethyl-4-hydroxybenzylidene-4-piperidone-and-related-compounds-induce-glutathione-oxidation-and-mitochondria-mediated-cell-death-in-hct-116-colon-cancer-cells
#18
Eshwari Addala, Hossein Rafiei, Swagatika Das, Brian Bandy, Umashankar Das, Subhas S Karki, Jonathan R Dimmock
This study aims at investigating the cytotoxicity and some of the modes of action of 3,5-bis(3-dimethylamino-4-hydroxybenzylidene)-4-piperidone trihydrochloride 3 and two related compounds 2 (which lacks the dimethylaminomethyl groups) and 4 (which has an additional dimethylaminoethyl substituent in both aryl rings) in order to ascertain the contribution of dimethylaminoethyl substituent to bioactivity. The bioactivities of 2-4 were compared with curcumin 5. Both 2 and 3 displayed submicromolar GI50 values towards HCT-116 cells and were significantly more potent than 4, 5 and 5-fluorouracil (5-FU)...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28716449/venom-derived-peptides-inhibiting-kir-channels-past-present-and-future
#19
REVIEW
Craig A Doupnik
Inwardly rectifying K+ (Kir) channels play a significant role in vertebrate and invertebrate biology by regulating the movement of K+ ions involved in membrane transport and excitability. Yet unlike other ion channels including their ancestral K + -selective homologs, there are very few venom toxins known to target and inhibit Kir channels with the potency and selectivity found for the Ca2+-activated and voltage-gated K+ channel families. It is unclear whether this is simply due to a lack of discovery, or instead a consequence of the evolutionary processes that drive the development of venom components towards their targets based on a collective efficacy to 1) elicit pain for defensive purposes, 2) promote paralysis for prey capture, or 3) facilitate delivery of venom components into the circulation...
July 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28715871/improvement-of-mitochondrial-function-by-celastrol-in-palmitate-treated-c2c12-myotubes-via-activation-of-pi3k-akt-signaling-pathway
#20
Mohamad Hafizi Abu Bakar, Joo Shun Tan
Compelling evidences posited that high level of saturated fatty acid gives rise to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. Celastrol is a pentacyclic triterpenoid derived from the root extracts of Tripterygium wilfordii that possesses potent anti-inflammatory properties in a number of animal models with metabolic diseases. However, the cellular mechanistic action of celastrol in alleviating obesity-induced insulin resistance in skeletal muscle remains largely unknown...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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