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https://www.readbyqxmd.com/read/28448574/fusion-expression-of-occludin-extracellular-loops-and-an-%C3%AE-helical-bundle-a-new-research-model-for-tight-junction
#1
Xiaojing Chi, Xia Zhao, Wei Wang, Yuqiang Niu, Min Cheng, Xiuying Liu, Sheng Cui, Wei Yang
Tight junctions (TJs) are the outermost structures of intercellular junctions and are highly specialized membrane domains involved in many important cellular processes. However, most TJ proteins are four-time transmembrane proteins and are difficult to express in their correct soluble form, which limits their functional study and therapeutic application. Human occludin (OCLN) is a major component of TJs and an essential co-receptor for hepatitis C virus (HCV) cell entry. To explore expression strategy for recombinant TJ proteins possessing integrated and functional extracellular loops, OCLN was here used as a model molecule, and several prokaryotic fusion constructs were designed by docking OCLN extracellular loops (ECLs) to HIV-1 gp41 NHR and CHR six-helical bundle (6HV1); then their biophysical features and anti-HCV activity were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28445950/the-discovery-of-a-novel-compound-with-potent-antitumor-activity-virtual-screening-synthesis-biological-evaluation-and-preliminary-mechanism-study
#2
Yuanyuan Jin, Linhu Li, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Weiyi Shen
Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC50s: 6.92-8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442414/inhibition-of-allogeneic-cytotoxic-t-cell-cd8-proliferation-via-polymer-induced-treg-cd4-cells
#3
Ning Kang, Wendy M Toyofuku, Xining Yang, Mark D Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8(+)) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8(+) and CD4(+) alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model...
April 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28440509/modulation-of-mmp-2-and-9-secretion-by-cytokines-inducers-and-inhibitors-in-human-melanoma-a-2058-cells
#4
M Waheed Roomi, Tatiana Kalinovsky, Aleksandra Niedzwiecki, Matthias Rath
Melanoma, an extremely aggressive cancer, causes the most skin cancer-related deaths, due to metastasis to other areas of the body, such as lymph nodes, lungs, liver, brain or bone. It is characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix and basement membrane, allowing cancer cells to spread to distal organs. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in regulation of MMP-2 and -9 in human melanoma A-2058 cells...
April 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440403/ginsenoside-rh2-and-rg3-inhibit-cell-proliferation-and-induce-apoptosis-by-increasing-mitochondrial-reactive-oxygen-species-in-human-leukemia-jurkat-cells
#5
Ting Xia, Ying-Nan Wang, Chuan-Xin Zhou, Li-Mei Wu, Yong Liu, Qian-Hong Zeng, Xiang-Long Zhang, Jia-Hui Yao, Min Wang, Jian-Pei Fang
Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell‑death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit‑8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP)...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28436935/tnf-superfamily-receptor-ox40-triggers-invariant-nkt-cell-pyroptosis-and-liver-injury
#6
Peixiang Lan, Yihui Fan, Yue Zhao, Xiaohua Lou, Howard P Monsour, Xiaolong Zhang, Yongwon Choi, Yaling Dou, Naoto Ishii, Rafik M Ghobrial, Xiang Xiao, Xian Chang Li
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436620/arginine-rich-peptide-based-mrna-nanocomplexes-efficiently-instigate-cytotoxic-t-cell-immunity-dependent-on-the-amphipathic-organization-of-the-peptide
#7
Vimal K Udhayakumar, Ans De Beuckelaer, Joanne McCaffrey, Cian M McCrudden, Jonathan L Kirschman, Daryll Vanover, Lien Van Hoecke, Kenny Roose, Kim Deswarte, Bruno G De Geest, Stefan Lienenklaus, Philip J Santangelo, Johan Grooten, Helen O McCarthy, Stefaan De Koker
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol...
April 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28436427/broad-and-potent-cross-clade-neutralizing-antibodies-with-multiple-specificities-in-the-plasma-of-hiv-1-subtype-c-infected-individuals
#8
Narayanaiah Cheedarla, K Lucia Precilla, Hemalatha Babu, K K Vidya Vijayan, Manickam Ashokkumar, Padmapriyadarsini Chandrasekaran, Nandagopal Kailasam, Jagadish Chandrabose Sundaramurthi, Soumya Swaminathan, Viswanath Buddolla, S Kalyanaraman Vaniambadi, V D Ramanathan, Luke Elizabeth Hanna
Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435886/discovery-of-a-novel-antifungal-agent-in-the-pathogen-box
#9
François L Mayer, James W Kronstad
Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with very high mortality rates. Patients with dysfunctional immune systems, such as individuals with HIV/AIDS, are particularly susceptible to fungal infections. Unfortunately, relatively few antifungal drugs are currently available and fungi frequently develop resistance, further complicating treatment approaches...
March 2017: MSphere
https://www.readbyqxmd.com/read/28431540/prevention-of-advanced-glycation-end-products-formation-in-diabetic-rats-through-beta-cell-modulation-by-aegle-marmelos
#10
Rahman M Hafizur, Shahrukh Momin, Noor Fatima
BACKGROUND: Although the anti-diabetic activity of Aegle marmelos (AM) is known, however, its anti-glycation activity is not reported yet. In this study, we have investigated its anti-glycation activity under in vitro and in vivo conditions and determined possible mechanism(s) in streptozotocin-induced diabetic rats. METHODS: Effective dose of AM (400 mg/kg) was administrated orally to diabetic rats for 42 days. Thereafter, blood glucose, serum insulin, HbA1c, antioxidant status, and advanced glycation end-products (AGEs) were measured...
April 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28430797/effect-of-quinoline-based-1-2-3-triazole-and-its-structural-analogues-on-growth-and-virulence-attributes-of-candida-albicans
#11
Mohammad Irfan, Shadab Alam, Nikhat Manzoor, Mohammad Abid
Candida albicans, along with some other non-albicans Candida species, is a group of yeast, which causes serious infections in humans that can be both systemic and superficial. Despite the fact that extensive efforts have been put into the discovery of novel antifungal agents, the frequency of these fungal infections has increased drastically worldwide. In our quest for the discovery of novel antifungal compounds, we had previously synthesized and screened quinoline containing 1,2,3-triazole (3a) as a potent Candida spp inhibitor...
2017: PloS One
https://www.readbyqxmd.com/read/28428950/endogenous-and-exogenous-kdpf-peptide-increases-susceptibility-of-mycobacterium-bovis-bcg-to-nitrosative-stress-and-reduces-intramacrophage-replication
#12
Mariana Rosas Olvera, Eric Vivès, Virginie Molle, Anne-Béatrice Blanc-Potard, Laila Gannoun-Zaki
Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium bovis BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28427443/benserazide-a-dopadecarboxylase-inhibitor-suppresses-tumor-growth-by-targeting-hexokinase-2
#13
Wei Li, Mengzhu Zheng, Shuangping Wu, Suyu Gao, Mei Yang, Zhimei Li, Qiuxia Min, Weiguang Sun, Lixia Chen, Guangya Xiang, Hua Li
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28426244/piperine-triggers-apoptosis-of-human-oral-squamous-carcinoma-through-cell-cycle-arrest-and-mitochondrial-oxidative-stress
#14
Sahabjada Siddiqui, Md Sultan Ahamad, Asif Jafri, Mohd Afzal, Md Arshad
Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine...
April 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28425077/unexpected-and-striking-effect-of-heparin-free-dialysis-on-cytokine-release
#15
Alicja Rydzewska-Rosolowska, Joanna Gozdzikiewicz-Lapinska, Jacek Borawski, Ewa Koc-Zorawska, Michal Mysliwiec, Beata Naumnik
Heparin (both unfractionated and low molecular weight) is not only a potent anticoagulant but also has many pleiotropic effects, some of which are mediated by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin as an anticoagulant and without systemic anticoagulation (heparin-grafted membrane-Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1), endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured after such a dialysis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28424618/pharmacological-and-biochemical-characterization-of-tlqp-21-activation-of-a-binding-site-on-cho-cells
#16
Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Pamela Petrocchi Passeri, Corrado Ghè, Giampiero Muccioli, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Anna Binda, Ilaria Rivolta, Vittorio Locatelli, Antonio Torsello
VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF(556-576)) has raised a huge interest and is one of most studied. TLQP-21 is a multifunctional neuropeptide involved in the control of several physiological functions, potentially including energy homeostasis, pain modulation, stress responsiveness and reproduction...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424617/targeting-bile-acid-receptors-discovery-of-a-potent-and-selective-farnesoid-x-receptor-agonist-as-a-new-lead-in-the-pharmacological-approach-to-liver-diseases
#17
Carmen Festa, Simona De Marino, Adriana Carino, Valentina Sepe, Silvia Marchianò, Sabrina Cipriani, Francesco S Di Leva, Vittorio Limongelli, Maria C Monti, Angela Capolupo, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
Bile acid (BA) receptors represent well-defined targets for the development of novel therapeutic approaches to metabolic and inflammatory diseases. In the present study, we report the generation of novel C-3 modified 6-ethylcholane derivatives. The pharmacological characterization and molecular docking studies for the structure-activity rationalization, allowed the identification of 3β-azido-6α-ethyl-7α-hydroxy-5β-cholan-24-oic acid (compound 2), a potent and selective FXR agonist with a nanomolar potency in transactivation assay and high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28423169/innate-immune-response-to-lipooligosaccharide-pivotal-regulator-of-the-pathobiology-of-invasive-neisseria-meningitidis-infections
#18
Constance M John, Nancy J Phillips, Daniel C Stein, Gary A Jarvis
Infections due to Neisseria meningitidis afflict more than one million people worldwide annually and cause death or disability in many survivors. The clinical course of invasive infections has been well studied, but our understanding of the cause of differences in patient outcomes has been limited because these are dependent on multiple factors including the response of the host, characteristics of the bacteria and interactions between the host and the bacteria. The meningococcus is a highly inflammatory organism, and the lipooligosaccharide (LOS) on the outer membrane is the most potent inflammatory molecule it expresses due to the interactions of the lipid A moiety of LOS with receptors of the innate immune system...
April 1, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28422508/nitrile-in-the-hole-discovery-of-a-small-auxiliary-pocket-in-neuronal-nitric-oxide-synthase-leading-to-the-development-of-potent-and-selective-2-aminoquinoline-inhibitors
#19
Maris A Cinelli, Huiying Li, Georges Chreifi, Thomas L Poulos, Richard B Silverman
Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat neurodegenerative disorders, but the development of nNOS inhibitors is often hindered by poor pharmacokinetics. We previously developed a class of membrane-permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to decrease off-target binding. However, the resulting compounds had decreased permeability, low human nNOS activity, and low selectivity versus human eNOS. In this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives were synthesized and assayed against purified NOS isoforms...
April 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28422390/naringin-abates-adverse-effects-of-cadmium-mediated-hepatotoxicity-an-experimental-study-using-hepg2-cells
#20
Visesh Kumar Rathi, Shubhankar Das, Archana Parampalli Raghavendra, Bola Sadashiva Satish Rao
This study investigated the protective potential of Naringin (NIN) against cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular carcinoma (HepG2) cells. An optimal concentration of NIN (5 μM) was potent enough to confer cytoprotection against CdCl2 (50 μM) as was observed by MTT assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial membrane potential, and reduced apoptosis as marked by decrease in the percentage sub-G0 /G1 and Annexin V-FITC/propidium iodide positive cells (apoptotic)...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
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