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https://www.readbyqxmd.com/read/27933593/inflammation-induced-cd69-kupffer-cell-feedback-inhibits-t-cell-proliferation-via-membrane-bound-tgf-%C3%AE-1
#1
Xiang Zhang, Zhengping Jiang, Yan Gu, Yanfang Liu, Xuetao Cao, Yanmei Han
Kupffer cells, tissue-resident macrophage lineage cell, are enriched in vertebrate liver. The mouse F4/80(+) Kupffer cells have been subclassified into two subpopulations according to their phenotype and function: CD68(+) subpopulation with potent reactive oxygen species (ROS) production and phagocytic capacities, and CD11b(+) subpopulation with a potent capacity to produce T helper 1 cytokines. In addition, CD11b(+) Kupffer cells/macrophages may be migrated from the bone marrow or spleen, especially in inflammatory conditions of the liver...
December 6, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27933340/enhancement-of-pharmacological-effects-of-uricosuric-agents-by-concomitant-treatment-with-pyrazinamide-in-rats
#2
Tetsuya Taniguchi, Naoki Ashizawa, Koji Matsumoto, Takashi Iwanaga
Our goal was to establish a model for the evaluation of the effects of uricosuric agents and to clarify the underlying mechanism(s). The effects of a uricosuric agent co-treated with pyrazinamide, an anti-tubercular agent, on urate handling were examined in rats. Furthermore, the effects of uricosuric agents on urate uptake were evaluated using the vesicles of rat renal brush-border membrane. Treatment with probenecid, at a dose of 100 mg/kg, significantly increased the urinary urate to creatinine ratio (UUA/UCRE) in pyrazinamide-treated rats although the same treatment did not produce any uricosuric effects in intact rats...
December 8, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27933037/blad-containing-oligomer-fungicidal-activity-on-human-pathogenic-yeasts-from-the-outside-to-the-inside-of-the-target-cell
#3
Ana M Pinheiro, Alexandra Carreira, Filipe Rollo, Rui Fernandes, Ricardo B Ferreira, Sara A Monteiro
Blad polypeptide comprises residues 109-281 of Lupinus albus β-conglutin precursor. It occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent and broad spectrum fungicide activity toward plant pathogens and is now on sale in the US under the tradename Fracture(TM). In this work we demonstrate its antifungal activity toward human pathogens and provide some insights on its mode of action...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932311/daclatasvir-prevents-hepatitis-c-virus-by-blocking-transfer-of-viral-genome-to-assembly-sites
#4
Bertrand Boson, Solène Denolly, Fanny Turlure, Christophe Chamot, Marlène Dreux, François-Loïc Cosset
BACKGROUND & AIMS: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs and inhibition of viral particle assembly...
December 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27931512/xenotransplanted-pig-sertoli-cells-inhibit-both-the-alternative-and-classical-pathways-of-complement-mediated-cell-lysis-while-pig-islets-are-killed
#5
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SCs) survive xenotransplantation long term (90 days) without immunosuppression, making SCs an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies and the activation of the complement cascade. Using an in vitro cytotoxicity assay, wherein cells were cultured with human serum and complement, we demonstrated that neonatal pig SCs (NPSCs) are resistant to complement-mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46), and decay-accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPIs), which served as non-immune-privileged controls...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27925693/identification-of-n-arylated-nh125-analogues-as-rapid-eradicating-agents-against-mrsa-persister-cells-and-potent-biofilm-killers-of-gram-positive-pathogens
#6
Yasmeen Abouelhassan, Akash Basak, Hussain Yousaf, Robert William Huigens Iii
Bacterial biofilms housing dormant persister cells are innately tolerant to antibiotics and disinfectants, yet several membrane-active agents are known to eradicate tolerant bacterial cells. NH125, a membrane-active persister-killer and starting point for development, led to the identification of N-arylated analogues 1 and 2 and displayed improved biofilm-killing potencies and rapid persister-killing activities in stationary cultures of methicillin-resistant Staphylococcus aureus (MRSA). We found 1 and 2 to be superior to other membrane-active agents in biofilm eradication assays with 1 demonstrating minimum biofilm eradication concentrations (MBEC) of 23...
December 7, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27925199/dopamine-dependent-effects-on-basal-and-glutamate-stimulated-network-dynamics-in-cultured-hippocampal-neurons
#7
Yan Li, Xin Chen, Rhonda Dzakpasu, Katherine Conant
Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine (DA), a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors (D1Rs) to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation (LTP) of excitatory synaptic transmission in striatum and prefrontal cortex...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27924931/global-proteomic-analysis-of-prenylated-proteins-in-plasmodium-falciparum-using-an-alkyne-modified-isoprenoid-analogue
#8
Kiall F Suazo, Chad Schaber, Charuta C Palsuledesai, Audrey R Odom John, Mark D Distefano
Severe malaria due to Plasmodium falciparum infection remains a serious threat to health worldwide and new therapeutic targets are highly desirable. Small molecule inhibitors of prenyl transferases, enzymes that catalyze the post-translational isoprenyl modifications of proteins, exhibit potent antimalarial activity. The antimalarial actions of prenyltransferase inhibitors indicate that protein prenylation is required for malaria parasite development. In this study, we used a chemical biology strategy to experimentally characterize the entire complement of prenylated proteins in the human malaria parasite...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923747/ibulocydine-sensitizes-human-hepatocellular-carcinoma-cells-to-trail-induced-apoptosis-via-calpain-mediated-bax-cleavage
#9
Seok Soon Park, Eunjin Jwa, Seol Hwa Shin, Eun Jin Ju, Intae Park, Jhang Ho Pak, Jung Jin Hwang, Dong-Hyung Cho, B Moon Kim, Sung-Bae Kim, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells without affecting the majority of normal human cells. However, hepatocellular carcinoma (HCC) cells often display resistance to TRAIL-induced apoptosis. Ibulocydine (IB) is an isobutyrate ester pro-drug of a novel synthetic Cdk inhibitor that targets Cdk7 and Cdk9. In this study, we show that treatment with subtoxic doses of IB in combination with TRAIL displays potent cytotoxicity in TRAIL-resistant human HCC cells...
December 3, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27919962/ascorbyl-stearate-promotes-apoptosis-through-intrinsic-mitochondrial-pathway-in-hela-cancer-cells
#10
Shirish D Mane, Maikho Thoh, Deepak Sharma, Santosh K Sandur, K Akhilender Naidu
BACKGROUND: Ascorbic acid is proposed to have antitumor potential against certain cancer types but has the limitation of requiring high doses for treating cancer. Ascorbyl stearate (ASC-S) is a fatty acid ester derivative of ascorbic acid with comparable potent apoptotic activity. The present study was aimed at understanding the pathway involved in apoptotic activity of ASC-S in cervical cancer cells. MATERIALS AND METHODS: The effect of ASC-S on reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) was studied in HeLa cells...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27917408/prostate-specific-membrane-antigen-targeted-polymersomes-for-delivering-mocetinostat-and-docetaxel-to-prostate-cancer-cell-spheroids
#11
Fataneh Karandish, Manas K Haldar, Seungyong You, Amanda E Brooks, Benjamin D Brooks, Bin Guo, Yongki Choi, Sanku Mallik
Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat...
November 30, 2016: ACS Omega
https://www.readbyqxmd.com/read/27915018/design-and-surface-immobilization-of-short-anti-biofilm-peptides
#12
Biswajit Mishra, Tamara Lushnikova, Radha M Golla, Xiuqing Wang, Guangshun Wang
: Short antimicrobial peptides are essential to keep us healthy and their lasting potency can inspire the design of new types of antibiotics. This study reports the design of a family of eight-residue tryptophan-rich peptides (TetraF2W) obtained by converting the four phenylalanines in temporin-SHf to tryptophans. The temporin-SHf template was identified from the antimicrobial peptide database (http://aps.unmc.edu/AP). Remarkably, the double arginine variant (TetraF2W-RR) was more effective in killing methicillin-resistant Staphylococcus aureus (MRSA) USA300, but less cytotoxic to human skin HaCat and kidney HEK293 cells, than the lysine-containing dibasic combinations (KR, RK and KK)...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27914690/c1q-as-an-autocrine-and-paracrine-regulator-of-cellular-functions
#13
REVIEW
Berhane Ghebrehiwet, Kinga H Hosszu, Ellinor I B Peerschke
Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes"...
November 30, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27914086/killing-bacteria-with-cytotoxic-effector-proteins-of-human-killer-immune-cells-granzymes-granulysin-and-perforin
#14
Diego López León, Isabelle Fellay, Pierre-Yves Mantel, Michael Walch
Bacterial pathogens represent a constant threat to human health that was exacerbated in recent years by a dramatic increase of strains resistant to last resort antibiotics. The immune system of higher vertebrates generally evolved several efficient innate and adaptive mechanisms to fight ubiquitous bacterial pathogens. Among those mechanisms, immune proteases were recognized to contribute essentially to antibacterial immune defense. The effector serine proteases of the adaptive immune system, the granzymes, exert potent antimicrobial activity when they are delivered into the bacterial cytosol by prokaryotic membrane disrupting proteins, such as granulysin...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27912879/how-do-the-alkaloids-emetine-and-homoharringtonine-kill-trypanosomes-an-insight-into-their-molecular-modes-of-action
#15
Sonja Krstin, Tamer Mohamed, Xiaojuan Wang, Michael Wink
BACKGROUND: Although Trypanosoma brucei causes deadly sleeping sickness, the number of the registered medications is rather limited. Some plant alkaloids are potent trypanocidal agents. PURPOSE: In this study, we wanted to elucidate the molecular modes of trypanocidal activity of the alkaloids emetine and homoharringtonine against Trypanosoma brucei brucei. METHODS: We investigated the activity of both alkaloids regarding growth recovery from alkaloid-induced stress...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#16
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910159/staphylococcus-aureus-derived-membrane-vesicles-exacerbate-skin-inflammation-in-atopic-dermatitis
#17
S H Jun, J H Lee, S I Kim, C W Choi, T I Park, H R Jung, J W Cho, S H Kim, J C Lee
BACKGROUND: Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. OBJECTIVE: We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. METHODS: Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27908752/n-propargylpiperidines-with-naphthalene-2-carboxamide-or-naphthalene-2-sulfonamide-moieties-potential-multifunctional-anti-alzheimer-s-agents
#18
Urban Košak, Damijan Knez, Nicolas Coquelle, Boris Brus, Anja Pišlar, Florian Nachon, Xavier Brazzolotto, Janko Kos, Jacques-Philippe Colletier, Stanislav Gobec
In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#19
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#20
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
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