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https://www.readbyqxmd.com/read/29342415/lysosomes-targeting-imaging-and-anticancer-properties-of-novel-bis-naphthalimide-derivatives
#1
Rui-Xue Rong, Shan-Shan Wang, Xuan Liu, Ren-Feng Li, Ke-Rang Wang, Zhi-Ran Cao, Xiao-Liu Li
A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803 cells were investigated, Compounds NI1-NI4 modified with piperidine and piperazine exhibited good and selective cytotoxic activity, for instance, compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC-803 cells with the IC50 values of 2.89, 060, 2...
January 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29342295/empagliflozin-treatment-is-associated-with-improved-beta-cell-function-in-t2dm
#2
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
Objective: To examine whether lowering the plasma glucose concentration with empagliflozin (SGLT2 inhibitor) improves beta cell function in T2DM. Research Design and Methods: 15 T2DM patients received empagliflozin (25 mg/day) for 2 weeks, and beta cell function was measured with 9-step hyperglycemic clamp (each step = +40 mg/dl) before and 48 hours and 14 days after empagliflozin. Results: Empagliflozin caused 101±10 and 117±11 grams glucosuria on days 1 and 14 and produced 25±6 and 38±8 mg/dl reduction (p<0...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29342239/hplc-estimation-ex-vivo-everted-sac-permeability-and-in-vivo-pharmacokinetic-studies-of-darunavir
#3
Vasanti M Suvarna, Preeti C Sangave
Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic reversed-phase HPLC method was developed to monitor concentration of darunavir in in vitro intestinal fluid samples in everted sac absorption model in the presence of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated and successfully applied to everted sac and pharmacokinetic studies in rats. The absorption profiles of DRV and apparent permeability coefficients were determined...
January 12, 2018: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/29342227/brain-cytosolic-phospholipase-a2%C3%AE-mediates-angiotensin-ii-induced-hypertension-and-reactive-oxygen-species-production-in-male-mice
#4
Chi Young Song, Nayaab S Khan, Francesca-Fang Liao, Bin Wang, Ji Soo Shin, Joseph V Bonventre, Kafait U Malik
Background: Recently we reported that angiotensin II (Ang II)-induced hypertension is mediated by group IV cytosolic phospholipase A2α (cPLA2α) via production of pro-hypertensive eicosanoids. Since Ang II increases blood pressure via its action in the subfornical organ (SFO), it led us to investigate the expression and possible contribution of cPLA2α to oxidative stress and development of hypertension in this brain area. Methods: Adenovirus (Ad)-green fluorescence protein (GFP) cPLA2α short hairpin (sh) RNA (Ad-cPLA2α shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence protein cPLA2α DNA (Ad-cPLA2α DNA) and its control Ad-GFP DNA were transduced into SFO of cPLA2α+/+ and cPLA2α-/- male mice, respectively...
January 12, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#5
Zuzana Papackova, Marie Heczkova, Helena Dankova, Eva Sticova, Alena Lodererova, Lenka Bartonova, Martin Poruba, Monika Cahova
Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination...
2018: PloS One
https://www.readbyqxmd.com/read/29342201/differentiation-of-glioblastoma-multiforme-metastases-and-primary-central-nervous-system-lymphomas-using-multiparametric-perfusion-and-diffusion-mr-imaging-of-a-tumor-core-and-a-peritumoral-zone-searching-for-a-practical-approach
#6
Małgorzata Neska-Matuszewska, Joanna Bladowska, Marek Sąsiadek, Anna Zimny
INTRODUCTION: In conventional MR examinations glioblastomas multiforme (GBMs), metastases and primary CNS lymphomas (PCNSLs) may show very similar appearance. The aim of the study was to evaluate usefulness of multiparametric T2*DSC perfusion and diffusion MR imaging in the preoperative differentiation of these tumors. MATERIAL AND METHODS: Seventy four solitary enhancing tumors (27 GBMs, 30 metastases, 17 PCNSLs) were enrolled in the study. Parameters of cerebral blood volume (rCBV), peak height (rPH), percentage of signal recovery (rPSR) and apparent diffusion coefficient (ADC) were assessed from the tumor core and the peritumoral non-enhancing T2-hyperintense zone...
2018: PloS One
https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#7
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29342197/molecular-discrimination-of-tall-fescue-morphotypes-in-association-with-festuca-relatives
#8
Shyamal K Talukder, Perumal Azhaguvel, Konstantin Chekhovskiy, Malay C Saha
Tall fescue (Festuca arundinacea Schreb.) is an important cool-season perennial grass species used as forage and turf, and in conservation plantings. There are three morphotypes in hexaploid tall fescue: Continental, Mediterranean and Rhizomatous. This study was conducted to develop morphotype-specific molecular markers to distinguish Continental and Mediterranean tall fescues, and establish their relationships with other species of the Festuca genus for genomic inference. Chloroplast sequence variation and simple sequence repeat (SSR) polymorphism were explored in 12 genotypes of three tall fescue morphotypes and four Festuca species...
2018: PloS One
https://www.readbyqxmd.com/read/29342189/the-microbiota-metabolite-indole-inhibits-salmonella-virulence-involvement-of-the-phopq-two-component-system
#9
Nandita Kohli, Zeni Crisp, Rebekah Riordan, Michael Li, Robert C Alaniz, Arul Jayaraman
The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells...
2018: PloS One
https://www.readbyqxmd.com/read/29342185/nanocarrier-mediated-foliar-zinc-fertilization-influences-expression-of-metal-homeostasis-related-genes-in-flag-leaves-and-enhances-gluten-content-in-durum-wheat
#10
Paresh Deshpande, Ashwin Dapkekar, Manoj Oak, Kishore Paknikar, Jyutika Rajwade
BACKGROUND: Wheat is the staple food for most of the world's population; however, it is a poor source of zinc. Foliar fertilization of zinc via zinc loaded chitosan nanocarriers (Zn-CNP) post-anthesis has proved to be a promising approach for grain zinc enhancement in durum wheat as evidenced in our earlier study. However, the molecular mechanism of uptake of zinc via Zn-CNP remains unclear. METHODS/PRINCIPLE FINDINGS: Foliar application of Zn-CNP was performed at post anthesis stages in two durum wheat cultivars (MACS 3125 and UC1114, containing the Gpc-B1 gene), and expression levels of several metal-related genes were analyzed during early senescence...
2018: PloS One
https://www.readbyqxmd.com/read/29342181/optimization-of-mneongreen-for-homo-sapiens-increases-its-fluorescent-intensity-in-mammalian-cells
#11
Emiko Tanida-Miyake, Masato Koike, Yasuo Uchiyama, Isei Tanida
Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter...
2018: PloS One
https://www.readbyqxmd.com/read/29342161/association-between-circulating-levels-of-sex-steroid-hormones-and-esophageal-adenocarcinoma-in-the-finbar-study
#12
Jessica L Petrick, Roni T Falk, Paula L Hyland, Patrick Caron, Ruth M Pfeiffer, Shannon N Wood, Sanford M Dawsey, Christian C Abnet, Philip R Taylor, Chantal Guillemette, Liam J Murray, Lesley A Anderson, Michael B Cook
BACKGROUND: Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. METHODS: Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland...
2018: PloS One
https://www.readbyqxmd.com/read/29342151/cd8-signaling-in-microglia-macrophage-m1-polarization-in-a-rat-model-of-cerebral-ischemia
#13
Jan Boddaert, Kenny Bielen, Bart 's Jongers, Ekta Manocha, Laetitia Yperzeele, Patrick Cras, Daniel Pirici, Samir Kumar-Singh
Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke...
2018: PloS One
https://www.readbyqxmd.com/read/29342148/a-strong-summer-phytoplankton-bloom-southeast-of-vietnam-in-2007-a-transitional-year-from-el-ni%C3%A3-o-to-la-ni%C3%A3-a
#14
Hui Zhao, Jian Zhao, Xingli Sun, Fajin Chen, Guoqi Han
Summer upwelling occurs frequently off the southeast Vietnam coast in the western South China Sea (SCS), where summer phytoplankton blooms generally appear during June-August. In this study, we investigate inter-annual variation of Ekman pumping and offshore transport, and its modulation on summer blooms southeast of Vietnam. The results indicate that there are low intensities of summer blooms in El Niño years, under higher sea surface temperatures (SST) and weaker winds. However, a different pattern of monthly chlorophyll a (Chl-a) blooms occurred in summer of 2007, a transitional stage from El Niño to La Niña, with weak (strong) wind and high (low) SST before (after) early July...
2018: PloS One
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#15
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342135/structures-of-%C3%AE-klotho-reveal-a-zip-code-like-mechanism-for-endocrine-fgf-signalling
#16
Sangwon Lee, Jungyuen Choi, Jyotidarsini Mohanty, Leiliane P Sousa, Francisco Tome, Els Pardon, Jan Steyaert, Mark A Lemmon, Irit Lax, Joseph Schlessinger
Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through paracrine or autocrine mechanisms in a process that requires cooperation with heparan sulfate proteoglycans, which function as co-receptors for FGFR activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating hormones that regulate critical metabolic processes in a variety of tissues. FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates insulin sensitivity, energy expenditure and weight loss...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342133/a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#17
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342127/enhancement-in-corneal-permeability-of-dissolved-carteolol-by-its-combination-with-magnesium-hydroxide-nanoparticles
#18
Noriaki Nagai, Sakie Yamaoka, Yuya Fukuoka, Miyu Ishii, Hiroko Otake, Kazutaka Kanai, Norio Okamoto, Yoshikazu Shimomura
We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5% mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and MH particles...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#19
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342119/novel-hybrid-formulations-based-on-thiourea-derivatives-and-core-shell-fe%C3%A2-o%C3%A2-c18-nanostructures-for-the-development-of-antifungal-strategies
#20
Carmen Limban, Alexandru Vasile Missir, Miron Teodor Caproiu, Alexandru Mihai Grumezescu, Mariana Carmen Chifiriuc, Coralia Bleotu, Luminita Marutescu, Marius Toma Papacocea, Diana Camelia Nuta
The continuously increasing global impact of fungal infections is requiring the rapid development of novel antifungal agents. Due to their multiple pharmacological activities, thiourea derivatives represent privileged candidates for shaping new drugs. We report here the preparation, physico-chemical characterization and bioevaluation of hybrid nanosystems based on new 2-((4-chlorophenoxy)methyl)-N-(substituted phenylcarbamo-thioyl)benzamides and Fe₃O₄@C18 core@shell nanoparticles. The new benzamides were prepared by an efficient method, then their structure was confirmed by spectral studies and elemental analysis and they were further loaded on Fe₃O₄@C18 nanostructures...
January 17, 2018: Nanomaterials
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