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https://www.readbyqxmd.com/read/28441548/ferrocenyl-and-organic-novobiocin-derivatives-synthesis-and-their-in-vitro-biological-activity
#1
Mziyanda Mbaba, Amanda N Mabhula, Natasha Boel, Adrienne L Edkins, Michelle Isaacs, Heinrich C Hoppe, Setshaba D Khanye
A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f...
April 13, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28440745/primaquine-in-plasma-and-methemoglobinemia-in-patients-with-malaria-due-to-plasmodium-vivax-in-the-brazilian-amazon-basin
#2
José Luiz Vieira, Michelle E S Ferreira, Michelle V D Ferreira, Margarete M Gomes
Primaquine is the only licensed drug available for the elimination of Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the course of treatment. There is evidence that metabolites of primaquine formed by the cytochrome pathway are responsible for methemoglobin formation; a genetic polymorphism of cytochrome isoforms; and a potential influence of gender in the activities of these enzymes requiring the establishment of dose × response curves profiles in different population groups. Concentrations of primaquine in plasma and methemoglobin levels were investigated in 54 patients with malaria due to P...
April 3, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28438929/molecular-profile-of-malaria-drug-resistance-markers-of-plasmodium-falciparum-in-suriname
#3
Stella M Chenet, Sheila Akinyi Okoth, Julia Kelley, Naomi Lucchi, Curtis S Huber, Stephen Vreden, Alexandre Macedo de Oliveira, John W Barnwell, Venkatachalam Udhayakumar, Malti R Adhin
In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum We genotyped the PfK13 propeller domain of P. falciparum in forty samples as well as other mutations proposed to be associated with artemisinin resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia but we found fixed resistance mutations for chloroquine and sulfadoxine-pyrimethamine...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438834/rankl-cytokine-enhances-tnf-induced-osteoclastogenesis-independently-of-tnf-receptor-associated-factor-traf-6-by-degrading-traf3-in-osteoclast-precursors
#4
Zhenqiang Yao, Wei Lei, Rong Duan, Yanyun Li, Lu Luo, Brendan F Boyce
Cytokines, including receptor activator of nuclear factor kappa B ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro. However, the molecular mechanisms involved remain incompletely understood...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438197/anti-malarial-landscape-in-myanmar-results-from-a-nationally-representative-survey-among-community-health-workers-and-the-private-sector-outlets-in-2015-2016
#5
Si Thu Thein, Hnin Su Su Khin, Aung Thi
BACKGROUND: In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030. METHODS: This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28438155/the-malaria-testing-and-treatment-landscape-in-the-southern-lao-people-s-democratic-republic-pdr
#6
Saysana Phanalasy
BACKGROUND: In the context of national and regional goals to eliminate malaria by 2030, the Center for Malaria Parasitology and Entomology in the Lao PDR is implementing strategies to ensure all malaria cases are detected and appropriately treated with first-line artemisinin combination therapy, artemether-lumefantrine (AL). Timely and relevant evidence to inform policies and strategies is needed to ensure the most effective and efficient use of resources, and to accelerate progress towards elimination goals...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28438137/case-report-of-plasmodium-ovale-curtisi-malaria-in-sri-lanka-relevance-for-the-maintenance-of-elimination-status
#7
Sharmini Gunawardena, Rachel F Daniels, Thishan C Yahathugoda, Mirani V Weerasooriya, Katelyn Durfee, Sarah K Volkman, Dyann F Wirth, Nadira D Karunaweera
BACKGROUND: Following its recent certification as malaria-free, imported infections now pose the greatest threat for maintaining this status in Sri Lanka. Imported infections may also introduce species that are uncommon or not previously endemic to these areas. We highlight in this case report the increasing importance of less common malaria species such as Plasmodium ovale in elimination settings and discuss its relevance for the risk of malaria resurgence in the country. CASE PRESENTATION: A 41-year-old patient from southern Sri Lanka was diagnosed with malaria after 8 days of fever...
April 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28435460/size-dependent-effects-of-gold-nanoparticles-on-osteogenic-differentiation-of-human-periodontal-ligament-progenitor-cells
#8
Yangheng Zhang, Na Kong, Yuanchao Zhang, Wenrong Yang, Fuhua Yan
Gold nanoparticles (AuNPs) have been reported to promote osteogenic differentiation of mesenchymal stem cells and osteoblasts, but little is known about their effects on human periodontal ligament progenitor cells (PDLPs). In this study, we evaluated the effects of AuNPs with various diameters (5, 13 and 45 nm) on the osteogenic differentiation of PDLPs and explored the underlying mechanisms. 5 nm AuNPs reduced the alkaline phosphatase activity, mineralized nodule formation and expression of osteogenic genes, while 13 and 45 nm AuNPs increased these osteogenic markers...
2017: Theranostics
https://www.readbyqxmd.com/read/28433888/plasma-derived-exosomes-contribute-to-inflammation-via-the-tlr9-nf-%C3%AE%C2%BAb-pathway-in-chronic-heart-failure-patients
#9
Wei Ye, Xiaojun Tang, Zhengquan Yang, Chu Liu, Xin Zhang, Jing Jin, Jianxin Lyu
Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#10
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#11
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28427998/nitric-oxide-regulated-proteolysis-of-human-cyp2b6-via-the-ubiquitin-proteasome-system
#12
Choon-Myung Lee, Shweta Tripathi, Edward T Morgan
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427418/immunity-as-a-predictor-of-anti-malarial-treatment-failure-a-systematic-review
#13
Katherine O'Flaherty, Julia Maguire, Julie A Simpson, Freya J I Fowkes
BACKGROUND: Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure. METHODS: Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#14
Jiaqiu Li, Ping Song, Liyuan Zhu, Neelum Aziz, Qiyin Zhou, Yulong Zhang, Wenxia Xu, Lifeng Feng, Dingwei Chen, Xian Wang, Hongchuan Jin
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421659/the-anti-inflammatory-effects-of-morin-hydrate-in-atherosclerosis-is-associated-with-autophagy-induction-through-camp-signaling
#15
Yue Zhou, Zhan-Qi Cao, Hong-Yuan Wang, Yan-Na Cheng, Lu-Gang Yu, Xin-Ke Zhang, Yan Sun, Xiu-Li Guo
SCOPE: Although the previous trials of inflammation have indicated that morin hydrate (MO) hold considerable promise, understanding the distinct mechanism of MO against inflammation remains a challenge. METHODS AND RESULTS: This study investigated the effect of MO in atherosclerosis in ApoE(-/-) mice and underlying cell signaling of MO effect in inflammation in human umbilical vein endothelial cells (HUVECs). Administration of MO significantly reduced serum lipid level, inflammatory cytokines (TNF-α and ICAM-1) and atherosclerotic plaque formation in vivo...
April 18, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28420430/chronic-stress-induces-cd99-suppresses-autophagy-and-affects-spontaneous-adipogenesis-in-human-bone-marrow-stromal-cells
#16
Zvenyslava Husak, Michael N Dworzak
BACKGROUND: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent cells with a high constitutive level of autophagy and low expression of CD99. Under certain conditions, MSCs may develop tumorigenic properties. However, these transformation-induced conditions are largely unknown. Recently, we have identified an association between Hsp70, a main participant in cellular stress response and tumorigenesis, and CD99. Preliminary observations had revealed upregulation of both proteins in stressed long-term cultured MSCs...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28420403/molecular-surveillance-of-plasmodium-falciparum-drug-resistance-in-the-republic-of-congo-four-and-nine-years-after-the-introduction-of-artemisinin-based-combination-therapy
#17
Felix Koukouikila-Koussounda, Sankarganesh Jeyaraj, Christian N Nguetse, Charles Nchotebah Nkonganyi, Kossiwa Clarisse Kokou, Mandingha K Etoka-Beka, Francine Ntoumi, Thirumalaisamy P Velavan
BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120)...
April 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28417340/preconditioning-of-primary-human-renal-proximal-tubular-epithelial-cells-without-tryptophan-increases-survival-under-hypoxia-by-inducing-autophagy
#18
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Hypoxia plays a significant role in the pathogenesis of acute kidney injury (AKI). Autophagy protects from AKI. Amino acid deprivation induces autophagy. The effect of L-tryptophan depletion on survival and autophagy in cultures of renal proximal tubular epithelial cells (RPTECs) under hypoxia was evaluated. METHODS: RPTECs were preconditioned in a medium containing or not tryptophan, following culture under hypoxia and treatment with or without the autophagy inhibitor chloroquine...
April 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28414310/autophagy-supports-generation-of-cells-with-high-cd44-expression-via-modulation-of-oxidative-stress-and-parkin-mediated-mitochondrial-clearance
#19
K A Whelan, P M Chandramouleeswaran, K Tanaka, M Natsuizaka, M Guha, S Srinivasan, D S Darling, Y Kita, S Natsugoe, J D Winkler, A J Klein-Szanto, R K Amaravadi, N G Avadhani, A K Rustgi, H Nakagawa
High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44(Low)-CD24(High) (CD44L) cells give rise to CD44(High)-CD24(-/Low) (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-β...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28410268/long-term-anti-itch-effect-of-botulinum-neurotoxin-a-is-associated-with-downregulation-of-trpv1-and-trpa1-in-the-dorsal-root-ganglia-in-mice
#20
Lei-Fang Cao, Meng Si, Ya Huang, Li-Hua Chen, Xiao-Yan Peng, Ya-Qin Qin, Teng-Teng Liu, Yan Zhou, Tong Liu, Wei-Feng Luo
Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice...
April 13, 2017: Neuroreport
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