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https://www.readbyqxmd.com/read/29684903/repurposing-itraconazole-to-the-benefit-of-skin-cancer-treatment-a-combined-azole-ddab-nanoencapsulation-strategy
#1
C Carbone, C Martins-Gomes, V Pepe, A M Silva, T Musumeci, G Puglisi, P M Furneri, E B Souto
In this work, we aimed at developing an improved topical SLN formulation combining itraconazole delivery with a coating layer of didodecyldimethylammonium bromide, thus repurposing the drug effectiveness by synergistic skin anticancer effectiveness. In order to obtain a stable SLN formulation with small homogeneously dispersed particles, a deep formulative study was developed screening three different solid lipids (Suppocire NB, Cetyl Palmitate and Dynasan 114) for the SLN preparation by the phase inversion temperature...
April 17, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29684860/polyphenol-rich-extract-of-ocimum-gratissimum-leaves-ameliorates-colitis-via-attenuating-colonic-mucosa-injury-and-regulating-pro-inflammatory-cytokines-production-and-oxidative-stress
#2
Quadri K Alabi, Rufus O Akomolafe, Joseph G Omole, Modinat A Adefisayo, Olaofe L Ogundipe, Ayodeji Aturamu, Joseph O Sanya
Colitis is a chronic inflammation and ulcer on the inner lining of the large intestine. For many centuries Ocimum gratissimum (OG) leaves have been used in folk medicine in Nigeria to treat inflammatory bowel diseases, however, to date, the anti-colitis effects of OG have not been scientifically proven. In this study we investigated the effects of polyphenol rich extract of Ocimum gratissimum (PREOG) leaf on colonic mucosa injury in colitis, its mechanisms, initial administration time and dosage. Dextran sodium sulfate (DSS)-induced rat colitis models was used...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29684847/the-association-between-p53-protein-phosphorylation-at-serine-15-serine-20-and-sensitivity-of-cells-isolated-from-patients-with-ovarian-cancer-and-cell-lines-to-chemotherapy-in-in-vitro-study
#3
Iwona Kamińska, Julia K Bar
BACKGROUND: The association between p53 protein phosphorylated at serine 15 (Ser15), serine 20 (Ser20) and ovarian tumor cell sensitivity after chemotherapy was analyzed in order to define the influence of p53 activation on tumor cell sensitivity to chemotherapy. METHODS: The study was performed on ovarian cancer cell line (OvBH-1), colon adenocarcinoma metastasis to ovary (SW626) and on cells isolated from ascitic fluids from patients with ovarian cancer: with (p53+) or without (p53-) p53 nuclear protein accumulation...
December 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29684687/arsenic-trioxide-inhibits-proliferation-and-induced-apoptosis-of-leukemia-stem-cells-with-drug-resistance
#4
Chunxia Liu, Hulai Wei, Xiaojian Yao, Bei Liu, Yaming Xi, Li Zhao
Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. K562/ADM cell, a leukemia resistant cell subtype, was used as leukemia multidrug resistant model to explore drug resistance of leukemia cells. We found that CD34+ CD38- , CD34+ CD38- CD123+ , cell surface markers of LSCs were significantly high expressed in K562/ADM cell, not in K562 cell with less drug resistance; compared with LSCs from K562, multidrug resistance protein P-gp and BCRP expression were significantly higher in K562/ADM cell...
March 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29684680/licochalcone-a-an-effective-and-low-toxicity-compound-against-toxoplasma-gondii-in-vitro-and-in-vivo
#5
Hongfei Si, Chunyan Xu, Jili Zhang, Xukun Zhang, Bing Li, Xuzheng Zhou, Jiyu Zhang
Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo. The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls...
March 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29684638/medication-related-osteonecrosis-of-the-jaw-a-survey-of-knowledge-attitudes-and-practices-among-dentists-in-the-principality-of-asturias-spain
#6
M Escobedo, L García-Consuegra, S Junquera, S Olay, G Ascani, L Junquera
INTRODUCTION: The objective of this study was to investigate the knowledge and capabilities of dentists and dental students in their last year of study in regard to risk factors of medication-related osteonecrosis of the jaw (MRONJ) in Spain. MATERIAL AND METHOD: We conducted a cross-sectional study consisting of a questionnaire survey in Asturias, Spain. The study was divided into three groups: dentists who worked for the public dental health care system (n=32), dentists who worked exclusively as private health care practitioners (n= 136), and dental students in their last year (year five) of study (n= 38)...
April 20, 2018: Journal of Stomatology, Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29684576/zd7288-and-mibefradil-inhibit-the-myogenic-heartbeat-in-daphnia-magna-indicating-its-dependency-on-hcn-and-t-type-calcium-ion-channels
#7
Thomas J Pirtle, Troy L Carr, Tanisha Khurana, Grace Meeker
Daphnia magna heartbeat is myogenic-originating within the animal's heart. However, the mechanism for this myogenic automaticity is unknown. The mechanism underlying the automaticity of vertebrate myogenic hearts involves cells (pacemaker cells), which have a distinct set of ion channels that include hyperpolarization activated cyclic nucleotide-gated (HCN) and T-type calcium ion channels. We hypothesized that these ion channels also underlie the automatic myogenic heartbeat of Daphnia magna. The drugs, ZD7288 and mibefradil dihydrochloride, block HCN and T-type calcium ion channels respectively...
April 20, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29684566/eltrombopag-for-the-treatment-of-of-refractory-pure-red-cell-aplasia-after-major-abo-incompatible-hematopoietic-stem-cell-transplantation
#8
Alessandro Busca, Chiara Dellacasa, Luisa Giaccone, Sara Manetta, Lucia Biale, Laura Godio, Semra Aydin, Moreno Festuccia, Lucia Brunello, Benedetto Bruno
Pure red cell aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, including erythropoietin, rituximab, bortezomib, plasma exchange, immunoadsorption, donor lymphocyte infusion, mesenchymal stem cells, anti-thymocyte globulin and high-dose steroids; however treatment outcomes are often variable and can sometimes lead to disappointing results. In this brief article we report our experience with two patients with PRCA after major AB0-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia (SAA), refractory to immunosuppressive agents or not eligible to HSCT...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684532/a-complicated-complex-ion-channels-voltage-sensing-cell-membranes-and-peptide-inhibitors
#9
REVIEW
Alan H Zhang, Gagan Sharma, Eivind A B Undheim, Xinying Jia, Mehdi Mobli
Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (NaV s) have attracted particular attention as potential analgesic targets. NaV s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e...
April 20, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29684343/crystal-structure-of-a-glutamate-1-semialdehyde-aminomutase-from-pseudomonas-aeruginosa-pao1
#10
Shanshan Li, Xiaorui Lou, Yueyang Xu, Xiaozhen Teng, Shiyou Che, Ruihua Liu, Mark Bartlam
The C5 pathway in bacteria is responsible for the synthesis of 5-aminolevulinic acid, which forms the core skeleton of cofactors required for metabolism. One of the key actors in this pathway is a pyridoxamine-5'-phosphate (PMP)/pyridoxal-5'-phosphate (PLP) dependent enzyme called glutamate-1-semialdehyde aminomutase (GSAM). In this study, we crystallized the expression product of the uncharacterized pa4088 gene from the opportunistic pathogen Pseudomonas aeruginosa PAO1. The resulting high-resolution structure confirms it to be a member of the GSAM family...
April 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29684096/toxic-effects-of-arsenic-trioxide-on-echinococcus-granulosus-protoscoleces-through-ros-production-and-ca2-er-stress-dependent-apoptosis
#11
Jiajie Li, Guangyao Tang, Wenjuan Qin, Rentan Yang, Rongji Ma, Bin Ma, Jianfeng Wei, Hailong Lv, Yufeng Jiang
Cystic echinococcosis is a severe parasitic disease that commonly affects the liver and causes abscesses or rupture into the surrounding tissues, leading to multiple complications, such as shock, severe abdominal pain, and post-treatment abscess recurrence. Currently, there are no efficient measures to prevent these complications. We previously confirmed that arsenic trioxide (As2O3) exhibited in vitro cytotoxicity against Echinococcus granulosus protoscoleces. In the present study, we aimed to explore the mechanism of As2O3-induced E...
April 19, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29684031/computationally-identified-novel-agonists-for-gprc6a
#12
Min Pi, Karan Kapoor, Ruisong Ye, Dong-Jin Hwang, Duane D Miller, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29683274/drug-repositioning-to-alleviate-systemic-inflammatory-response-syndrome-caused-by-gram-negative-bacterial-outer-membrane-vesicles
#13
Ji Hyun Kim, Jaewook Lee, Kyong-Su Park, Sung-Wook Hong, Yong Song Gho
Sepsis is characterized by systemic inflammatory response syndrome (SIRS) accompanied with infection. Gram-negative bacteria can evoke sepsis by activating the host immune system, such as the release of IL-6 and TNF-α, through their virulence factors. Outer membrane vesicles (OMVs), nanosized bilayered proteolipids derived from Gram-negative bacteria, harbor various virulence factors and are shown to induce SIRS. Here, drugs are repositioned to alleviate SIRS caused by Gram-negative bacterial OMVs. Using novel OMV-based drug screening systems, a total of 178 commercially available drugs are primarily screened, and a total of 18 repositioned drug candidates are found to effectively block IL-6 and TNF-α production from OMV-stimulated macrophages...
April 23, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29682820/plga-spherical-nucleic-acids
#14
Shengshuang Zhu, Hang Xing, Pavlo Gordiichuk, Jungsoo Park, Chad A Mirkin
A new class of polymer spherical nucleic acid (SNA) conjugates comprised of poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) cores is reported. The nucleic acid shell that defines the PLGA-SNA exhibits a half-life of more than 2 h in fetal bovine serum. Importantly, the PLGA-SNAs can be utilized to encapsulate a hydrophobic model drug, coumarin 6, which can then be released in a polymer composition-dependent tunable manner, while the dissociation rate of the nucleic acid shell remains relatively constant, regardless of core composition...
April 23, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29682747/contribution-of-equilibrative-nucleoside-transporters-1-and-2-to-gemcitabine-uptake-in-pancreatic-cancer-cells
#15
Masato Hioki, Takuya Shimada, Tian Yuan, Takeo Nakanishi, Hidehiro Tajima, Maiko Yamazaki, Rina Yokono, Makiko Takabayashi, Kazuki Sawamoto, Gaku Akashita, Ken-Ichi Miyamoto, Tetsuo Ohta, Ikumi Tamai, Tsutomu Shimada, Yoshimichi Sai
Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method to treat the hepatic metastasis of pancreatic cancer than intravenous (i.v.) administration because of higher tumor exposure and lower systemic exposure. To clarify the uptake mechanism of nucleoside anticancer drugs, including gemcitabine (GEM), in pancreatic cancer, we investigated the uptakes of radiolabeled uridine (a general substrate of nucleoside transporters) and GEM in pancreatic cancer cell lines MIA-PaCa2 and As-PC1...
April 22, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29682627/a-complier-average-causal-effect-analysis-of-the-stimulant-reduction-intervention-using-dosed-exercise-study
#16
Thomas Carmody, Tracy L Greer, Robrina Walker, Chad D Rethorst, Madhukar H Trivedi
Objective: Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. Method: The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U...
June 2018: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29682616/human-ccl3l1-copy-number-variation-gene-expression-and-the-role-of-the-ccl3l1-ccr5-axis-in-lung-function
#17
Adeolu B Adewoye, Nick Shrine, Linda Odenthal-Hesse, Samantha Welsh, Anders Malarstig, Scott Jelinsky, Iain Kilty, Martin D Tobin, Edward J Hollox, Louise V Wain
Background: The CCL3L1-CCR5 signaling axis is important in a number of inflammatory responses, including macrophage function, and T-cell-dependent immune responses. Small molecule CCR5 antagonists exist, including the approved antiretroviral drug maraviroc, and therapeutic monoclonal antibodies are in development. Repositioning of drugs and targets into new disease areas can accelerate the availability of new therapies and substantially reduce costs. As it has been shown that drug targets with genetic evidence supporting their involvement in the disease are more likely to be successful in clinical development, using genetic association studies to identify new target repurposing opportunities could be fruitful...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29682231/frequency-of-dementia-among-elderly-admitted-to-a-geriatrics-inpatients-sector-of-a-brazilian-public-hospital
#18
Rafael Thomazi, Liciana Vaz de Arruda Silveira, Paulo José Fortes Villas Boas, Alessandro Ferrari Jacinto
Patients with dementia are commonly admitted to inpatient sectors. The aim of this study was to describe the frequency of dementia among elderly inpatients admitted to the Geriatrics Sector of a Brazilian Tertiary University Hospital, and to identify associations between dementia and clinical and sociodemographic factors. Methods: All patients admitted to the Geriatrics Sector of a public Brazilian university-hospital from March 1st 2014 to January 31st 2015 were assessed by geriatricians...
January 2018: Dementia & Neuropsychologia
https://www.readbyqxmd.com/read/29682208/development-of-a-quantitative-pharmacodynamic-assay-for-apoptosis-in-fixed-tumor-tissue-and-its-application-in-distinguishing-cytotoxic-drug-induced-dna-double-strand-breaks-from-dna-double-strand-breaks-associated-with-apoptosis
#19
Angie B Dull, Deborah Wilsker, Melinda Hollingshead, Christina Mazcko, Christina M Annunziata, Amy K LeBlanc, James H Doroshow, Robert J Kinders, Ralph E Parchment
DNA double strand breaks (DSBs) induced by cancer therapeutic agents can lead to DNA damage repair or persistent DNA damage, which can induce apoptotic cell death; however, apoptosis also induces DSBs independent of genotoxic insult. γH2AX is an established biomarker for DSBs but cannot distinguish between these mechanisms. Activated cleaved caspase-3 (CC3) promotes apoptosis by enhancing nuclear condensation, DNA fragmentation, and plasma membrane blebbing. Here, we describe an immunofluorescence assay that distinguishes between apoptosis and drug-induced DSBs by measuring coexpression of γH2AX and membrane blebbing-associated CC3 to indicate apoptosis, and γH2AX in the absence of CC3 blebbing to indicate drug-induced DNA damage...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682185/stat5-inhibition-induces-trail-dr4-dependent-apoptosis-in-peripheral-t-cell-lymphoma
#20
Haley M Simpson, Aki Furusawa, Kavitha Sadashivaiah, Curt I Civin, Arnob Banerjee
Peripheral T-cell lymphoma (PTCL) is a rare, aggressive, heterogeneous, Non-Hodgkin's lymphoma with poor prognosis and inadequate response to current therapies. Recent sequencing studies indicate a prevalence of activating mutations in the JAK/STAT signaling pathway. Oncogenic mutations in STAT5B, observed in approximately one third of cases of multiple different PTCL subtypes, correlate with inferior patient outcomes. Therefore, interest in the development of therapeutic strategies for targeting STAT5 in PTCL is warranted...
March 30, 2018: Oncotarget
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