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https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#1
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29778697/structural-basis-for-selective-inhibition-of-antibacterial-target-mray-a-membrane-bound-enzyme-involved-in-peptidoglycan-synthesis
#2
REVIEW
Jenny Hering, Elin Dunevall, Margareta Ek, Gisela Brändén
The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase)...
May 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29776697/cinnamtannin-b-1-a-novel-antioxidant-for-sperm-in-red-deer
#3
F Sánchez-Rubio, M R Fernández-Santos, L Castro-Vázquez, O García-Álvarez, A Maroto-Morales, A J Soler, F Martínez-Pastor, J J Garde
Cinnamtannin B-1 (CNB-1) is a naturally occurring trimeric A-type proanthocyanidin contained in several plants such as cinnamon (Cinnamomum zeylanicum). It is considered to be a potent antioxidant. The protective effect of CNB-1 against oxidative stress was assessed in red deer epididymal sperm incubated at 37 °C. Cryopreserved sperm from six stags were thawed, pooled and extended to 400 × 106 sperm/ml in BGM (bovine gamete medium). After being aliquoted, the samples were supplemented with different concentrations of CNB-1 (0, 0...
May 15, 2018: Animal Reproduction Science
https://www.readbyqxmd.com/read/29774519/zika-virus-baculovirus-expressed-virus-like-particles-induce-neutralizing-antibodies-in-mice
#4
Shiyu Dai, Tao Zhang, Yanfang Zhang, Hualin Wang, Fei Deng
The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies...
May 17, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/29772356/assessment-of-toxicity-and-differential-antimicrobial-activity-of-methanol-extract-of-rhizome-of-simaba-ferruginea-a-st-hil-and-its-isolate-canthin-6-one
#5
Vanessa Fátima Gazoni, Sikiru Olaitan Balogun, Karuppusamy Arunacham, Darley Maria Oliveira, Valdir Cechinel Filho, Samara Rosolem Lima, Edson Moleta Colodel, Ilsamar Mendes Soares, Sérgio Donizeti Ascêncio, Domingos Tabajara de Oliveira Martins
ETHNOPHARMACOLOGICAL RELEVANCE: Simaba ferruginea A. St.-Hil., Simaroubaceae, popularly known as "calunga" is a typical subtropical shrub used in Central Brazil mainly for infection, anti-inflammatory, analgesic and gastric duodenal-ulcers. It presents in its composition the alkaloid canthin-6-one, an alkaloid indole β-carboxylic. AIM: This study aims to investigate the toxicity, antimicrobial activities of methanol extract of Simaba ferruginea (MESf) and canthin-6-one by using different experimental models...
May 14, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29770204/diverse-pro-inflammatory-endotoxin-recognition-systems-of-mammalian-innate-immunity
#6
REVIEW
Jerrold Weiss, Jason Barker
In humans and other mammals, recognition of endotoxins-abundant surface lipopolysaccharides (LPS) of Gram-negative bacteria-provides a potent stimulus for induction of inflammation and mobilization of host defenses. The structurally unique lipid A region of LPS is the principal determinant of this pro-inflammatory activity. This region of LPS is normally buried within the bacterial outer membrane and aggregates of purified LPS, making even more remarkable its picomolar potency and the ability of discrete variations in lipid A structure to markedly alter the pro-inflammatory activity of LPS...
2018: F1000Research
https://www.readbyqxmd.com/read/29766198/aquaporins-in-cancer-development-opportunities-for-bioinorganic-chemistry-to-contribute-novel-chemical-probes-and-therapeutic-agents
#7
REVIEW
Brech Aikman, Andreia de Almeida, Samuel M Meier-Menches, Angela Casini
Aquaporins (AQPs) are membrane proteins allowing permeation of water, glycerol & hydrogen peroxide across biomembranes, and playing an important role in water homeostasis in different organs, exocrine gland secretion, urine concentration, skin moisturization, fat metabolism and neural signal transduction. Notably, a large number of studies showed that AQPs are closely associated with cancer biological functions and expressed in more than 20 human cancer cell types. Furthermore, AQP expression is positively correlated with tumour types, grades, proliferation, migration, angiogenesis, as well as tumour-associated oedema, rendering these membrane channels attractive as both diagnostic and therapeutic targets in cancer...
May 16, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29766157/dual-acting-antitumor-pt-iv-prodrugs-of-kiteplatin-with-dichloroacetate-axial-ligands
#8
Salvatore Savino, Valentina Gandin, James D Hoeschele, Cristina Marzano, Giovanni Natile, Nicola Margiotta
With the aim to obtain dual acting drugs able to target both nuclear DNA and mitochondria, Pt(iv) kiteplatin derivatives having dichloroacetate (DCA) ligands in axial positions have been synthesized. The rather fast hydrolysis (t1/2 of ca. 1 h) and reduction (by ascorbic acid) of these Pt(iv) derivatives did not impede a potent pharmacological effect on tumor cells. Moreover, similarly to kiteplatin, also the Pt(iv)-DCA compounds proved to be capable of overcoming oxaliplatin-resistance, which is particularly important in view of the fact that metastatic colorectal cancer is the third most common cancer in males and the second in females...
May 16, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29765532/chemopreventive-activity-of-celastrol-in-drug-resistant-human-colon-carcinoma-cell-cultures
#9
Helena Moreira, Anna Szyjka, Kazimierz Gąsiorowski
Celastrol (tripterine) a pentacyclic triterpenoid extracted from the roots of Tripterygium wilfordii Hook f., exhibits potent antioxidant and anti-inflammatory activity and also exerts important anti-cancer effects, as induction of apoptosis and lowering the level of drug resistance of several cancers. Increased level of cellular resistance to cytostatic drugs is typical for colorectal cancers, and largely determines the failure of chemotherapy for this tumor. The purpose of our research was to evaluate the chemopreventive effect of celastrol on cultures of colon cancer cells resistant to doxorubicin (LOVO/DX)...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765509/resveratrol-induced-downregulation-of-naf-1-enhances-the-sensitivity-of-pancreatic-cancer-cells-to-gemcitabine-via-the-ros-nrf2-signaling-pathways
#10
Liang Cheng, Bin Yan, Ke Chen, Zhengdong Jiang, Cancan Zhou, Junyu Cao, Weikun Qian, Jie Li, Liankang Sun, Jiguang Ma, Qingyong Ma, Huanchen Sha
NAF-1 (nutrient-deprivation autophagy factor-1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29765497/di-2-pyridylhydrazone-dithiocarbamate-butyric-acid-ester-exerted-its-proliferative-inhibition-against-gastric-cell-via-ros-mediated-apoptosis-and-autophagy
#11
Xingshuang Guo, Yun Fu, Zhuo Wang, Tingting Wang, Cuiping Li, Tengfei Huang, Fulian Gao, Changzheng Li
Diversified biological activities of dithiocarbamates have attracted widespread attention; improving their feature or exploring their potent action of mechanism is a hot topic in medicinal research. Herein, we presented a study on synthesis and investigation of a novel dithiocarbamate, DpdtbA (di-2-pyridylhydrazone dithiocarbamate butyric acid ester), on antitumor activity. The growth inhibition assay revealed that DpdtbA had important antitumor activity for gastric cancer (GC) cell lines (IC50  = 4.2 ± 0...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29765373/compartmentalized-cyclic-amp-production-by-the-bordetella-pertussis-and-bacillus-anthracis-adenylate-cyclase-toxins-differentially-affects-the-immune-synapse-in-t-lymphocytes
#12
Vijay B Arumugham, Cristina Ulivieri, Anna Onnis, Francesca Finetti, Fiorella Tonello, Daniel Ladant, Cosima T Baldari
A central feature of the immune synapse (IS) is the tight compartmentalization of membrane receptors and signaling mediators that is functional for its ability to coordinate T cell activation. Second messengers centrally implicated in this process, such as Ca2+ and diacyl glycerol, also undergo compartmentalization at the IS. Current evidence suggests a more complex scenario for cyclic AMP (cAMP), which acts both as positive and as negative regulator of T-cell antigen receptor (TCR) signaling and which, as such, must be subjected to a tight spatiotemporal control to allow for signaling at the IS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29763807/positional-scanning-library-applied-to-the-human-eosinophil-cationic-protein-rnase3-n-terminus-reveals-novel-and-potent-anti-biofilm-peptides
#13
David Pulido, Guillem Prats-Ejarque, Clara Villalba, Marcel Albacar, Mohammed Moussaoui, David Andreu, Rudolf Volkmer, Marc Torrent, Ester Boix
Eradication of established biofilm communities of pathogenic bacteria is one of the pending challenges in the development of new antimicrobial agents. In particular, the dreaded nosocomial Pseudomonas aeruginosa forms microbial communities that offer an enhanced resistance to conventional antibiotics. Recently, we have described an engineered antimicrobial peptide derived from the human RNase3, also named the eosinophil cationic protein (ECP), RN3 (5-36), which combines bactericidal activity with high cell agglutination and lipopolysaccharide (LPS) affinity...
May 8, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29762783/repurposing-the-anthelminthic-salicylanilide-oxyclozanide-against-susceptible-and-clinical-resistant-candida-albicans-strains
#14
Emilie Pic, Anaïs Burgain, Adnane Sellam
Current antifungal drugs suffer from limitations including toxicity, adverse interactions with other commonly prescribed drugs, and the emergence of resistant strains. Here, we repurposed the anthelmintic oxyclozanide as a potent antifungal agent against both sensitive and resistant clinical isolates of Candida albicans, as well as other human opportunistic fungi. Antifungal activity of oxyclozanide was enhanced when C. albicans grew in nonfermentable carbon sources. Our data support a mechanism of action where oxyclozanide uncoupled the mitochondrial electron transport from oxidative phosphorylation and perturbed the mitochondrial membrane potential...
May 14, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29760660/ophiopogonin-d-a-natural-product-from-radix-ophiopogonis-induces-in-vitro-and-in-vivo-ripk1-dependent-and-caspase-independent-apoptotic-death-in-androgen-independent-human-prostate-cancer-cells
#15
Zongliang Lu, He Wang, Mingxing Zhu, Wei Song, Jiajia Wang, Changpeng Wu, Ya Kong, Jing Guo, Na Li, Jie Liu, Yanwu Li, Hongxia Xu
Objective: The purpose of this study was to evaluate the anticancer effects of Ophiopogonin D' (OPD', a natural product extracted from a traditional Chinese medicine ( Radix Ophiopogonis ) against androgen-independent prostate cancer cells and to explore the underlying molecular mechanism(s) of action. Methods: The CCK-8 assay was used to assess the viability of prostate cancer cells. The cell morphology was examined by an ultrastructural analysis via transmission electron microscopy. Cells in apoptosis (early and late stages) were detected using an Annexin V-FITC/propidium iodide kit with a FACSCaliber flow cytometer...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29758185/elucidating-the-bactericidal-mechanism-of-action-of-the-linear-antimicrobial-tetrapeptide-brbr-nh-2
#16
Qiu Ying Lau, Jianguo Li, Marc-Antoine Sani, Sheetal Sinha, Yan Li, Fui Mee Ng, CongBao Kang, Surajit Bhattacharjya, Frances Separovic, Chandra Verma, Cheng San Brian Chia
Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2 , with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution- and solid-state NMR spectroscopy followed by molecular dynamics simulations...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29753785/lactoferrin-inhibits-aflatoxin-b1-and-aflatoxin-m1-induced-cytotoxicity-and-dna-damage-in-caco-2-hek-hep-g2-and-sk-n-sh-cells
#17
Nan Zheng, Huan Zhang, Songli Li, Jiaqi Wang, Jia Liu, Hui Ren, Yanan Gao
Aflatoxins, including aflatoxin B1 (AFB1 ) and M1 (AFM1 ), are natural potent carcinogens produced by Aspergillus spp. These compounds, which can often be detected in dairy foods, can cause diseases in human beings. However, the molecular mechanisms involved in cytotoxicity, as well as methods for intervention, remain largely unexplored. For example, it is unclear whether lactoferrin (LF), a major antioxidant in milk, can inhibit the cytotoxicity of AFB1 and AFM1 . In this study, we assessed AFB1 - and AFM1 -induced cell toxicity by measuring cell viability, membrane permeability, and genotoxicity, and then investigated the ability of LF to protect cells against AFB1 and AFM1 ...
May 10, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29752618/tritium-labeled-agonists-as-tools-for-studying-adenosine-a-2b-receptors
#18
Sonja Hinz, Wessam M Alnouri, Ulrich Pleiss, Christa E Müller
A selective agonist radioligand for A2B adenosine receptors (A2B ARs) is currently not available. Such a tool would be useful for labeling the active conformation of the receptors. Therefore, we prepared BAY 60-6583, a potent and functionally selective A2B AR (partial) agonist, in a tritium-labeled form. Despite extensive efforts, however, we have not been able to establish a radioligand binding assay using [3 H]BAY 60-6583. This is probably due to its high non-specific binding and its moderate affinity, which had previously been overestimated based on functional data...
May 11, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29751611/purification-and-characterization-of-recombinant-botulinum-neurotoxin-serotype-fa-also-known-as-serotype-h
#19
Gavin Hackett, Kevin Moore, David Burgin, Fraser Hornby, Bryony Gray, Mark Elliott, Imran Mir, Matthew Beard
We have purified and characterized recombinant botulinum neurotoxin serotype FA (BoNT/FA). This protein has also been named as a new serotype (serotype H), but the classification has been controversial. A lack of well-characterized, highly pure material has been a roadblock to study. Here we report purification and characterization of enzymatically active, and of inactive nontoxic, recombinant forms of BoNT/FA as tractable alternatives to purifying this neurotoxin from native Clostridium botulinum . BoNT/FA cleaves the same intracellular target proteins as BoNT/F1 and other F serotype BoNTs; the intracellular targets are vesicle associated membrane proteins (VAMP) 1, 2 and 3...
May 11, 2018: Toxins
https://www.readbyqxmd.com/read/29750860/effect-of-composition-on-antibacterial-activity-of-sequence-defined-cationic-oligoteas
#20
Christine M Artim, Ngoc Nhu Phan, Christopher A Alabi
In response to the urgent need for new antibiotic development strategies, antimicrobial peptides and their synthetic mimetics are being investigated as promising alternatives to traditional antibiotics. To facilitate their development into clinically viable candidates, we need to understand what molecular features and physicochemical properties are needed to induce cell death. Within the context of sequence-defined oligothioetheramides (oligoTEAs), we explore the impact of the cationic pendant group and backbone hydrophobicity on the potency and selectivity of antibacterial oligoTEAs...
May 11, 2018: ACS Infectious Diseases
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