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Dihydroartemisinin

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https://www.readbyqxmd.com/read/28526807/dihydroartemisinin-induces-autophagy-dependent-death-in-human-tongue-squamous-cell-carcinoma-cells-through-dna-double-strand-break-mediated-oxidative-stress
#1
Xinli Shi, Li Wang, Xiaoming Li, Jing Bai, Jianchun Li, Shenghao Li, Zeming Wang, Mingrui Zhou
Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511713/artemisinin-based-combination-therapy-in-pregnant-women-in-zambia-efficacy-safety-and-risk-of-recurrent-malaria
#2
Michael Nambozi, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, David Mwakazanga, Joyce Mulenga, Webster Kasongo, Jozefien Buyze, Modest Mulenga, Jean-Pierre Van Geertruyden, Umberto D'Alessandro
BACKGROUND: In Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, the World Health Organization recommends the use of artemisinin-based combination therapy (ACT) in the second and third trimester of pregnancy. In a context of limited information on ACT, the safety and efficacy of three combinations, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS) and dihydroartemisinin-piperaquine (DHAPQ) were assessed in pregnant women with malaria...
May 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28506239/dihydroartemisinin-inhibits-tctp-dependent-metastasis-in-gallbladder-cancer
#3
Fei Zhang, Qiang Ma, Zihang Xu, Haibin Liang, Huaifeng Li, Yuanyuan Ye, Shanshan Xiang, Yijian Zhang, Lin Jiang, Yunping Hu, Zheng Wang, Xuefeng Wang, Yong Zhang, Wei Gong, Yingbin Liu
BACKGROUND: Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer. METHODS: Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins...
May 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28498397/dihydroartemisinin-inhibits-the-viability-of-cervical-cancer-cells-by-upregulating-caveolin%C3%A2-1-and-mitochondrial-carrier-homolog%C3%A2-2-involvement-of-p53-activation-and-nad-p-h-quinone-oxidoreductase%C3%A2-1-downregulation
#4
Ting Zhang, Yuan Hu, Ting Wang, Peiling Cai
Dihydroartemisinin (DHA) has been shown to inhibit the viability of various cancer cells. Previous studies have revealed that the mechanisms involved in the inhibitory effects of DHA are based on theactivation of p53 and the mitochondrial-related cell death pathway. However, the exact association between upstream signaling and the activation of cell death pathway remains unclear. In this study, we found that DHA treatment induced the upregulation of caveolin 1 (Cav1) and mitochondrial carrier homolog 2 (MTCH2) in HeLa cells, and this was associated with the DHA-induced inhibition of cell viability and DHA-induced apoptosis...
May 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28494763/artemisinin-resistance-without-pfkelch13-mutations-in-plasmodium-falciparum-isolates-from-cambodia
#5
Angana Mukherjee, Selina Bopp, Pamela Magistrado, Wesley Wong, Rachel Daniels, Allison Demas, Stephen Schaffner, Chanaki Amaratunga, Pharath Lim, Mehul Dhorda, Olivo Miotto, Charles Woodrow, Elizabeth A Ashley, Arjen M Dondorp, Nicholas J White, Dyann Wirth, Rick Fairhurst, Sarah K Volkman
BACKGROUND: Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance...
May 12, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28487425/a-variant-pfcrt-isoform-can-contribute-to-plasmodium-falciparum-resistance-to-the-first-line-partner-drug-piperaquine
#6
Satish K Dhingra, Devasha Redhi, Jill M Combrinck, Tomas Yeo, John Okombo, Philipp P Henrich, Annie N Cowell, Purva Gupta, Matthew L Stegman, Jonathan M Hoke, Roland A Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J Egan, David A Fidock
Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28480232/artemether-lumefantrine-and-dihydroartemisinin-piperaquine-exert-inverse-selective-pressure-on-plasmodium-falciparum-drug-sensitivity-associated-haplotypes-in-uganda
#7
Aimee R Taylor, Jennifer A Flegg, Chris C Holmes, Philippe J Guérin, Carol H Sibley, Melissa D Conrad, Grant Dorsey, Philip J Rosenthal
BACKGROUND: Altered sensitivity to multiple antimalarial drugs is mediated by polymorphisms in pfmdr1, which encodes the Plasmodium falciparum multidrug resistance transporter. In Africa the N86Y and D1246Y polymorphisms have been shown to be selected by treatment, with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) selecting for wild-type and mutant alleles, respectively. However, there has been little study of pfmdr1 haplotypes, in part because haplotype analyses are complicated by multiclonal infections...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28479604/codelivery-of-dihydroartemisinin-and-doxorubicin-in-mannosylated-liposomes-for-drug-resistant-colon-cancer-therapy
#8
Xue-Jia Kang, Hui-Yuan Wang, Hui-Ge Peng, Bin-Fan Chen, Wen-Yuan Zhang, Ai-Hua Wu, Qin Xu, Yong-Zhuo Huang
Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes)...
May 8, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28460112/baseline-in-vivo-ex-vivo-and-molecular-responses-of-plasmodium-falciparum-to-artemether-and-lumefantrine-in-three-endemic-zones-for-malaria-in-colombia
#9
Samanda Aponte, Ángela Patricia Guerra, Catalina Álvarez-Larrotta, Sindy Durley Bernal, César Restrepo, Camila González, María Fernanda Yasnot, Angélica Knudson-Ospina
Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days...
February 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28449690/daily-home-fortification-with-iron-as-ferrous-fumarate-versus-nafeedta-a-randomised-placebo-controlled-non-inferiority-trial-in-kenyan-children
#10
Emily M Teshome, Pauline E A Andang'o, Victor Osoti, Sofie R Terwel, Walter Otieno, Ayşe Y Demir, Andrew M Prentice, Hans Verhoef
BACKGROUND: We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. METHODS: We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L...
April 28, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28427409/efficacies-of-dha-ppq-and-as-sp-in-patients-with-uncomplicated-plasmodium-falciparum-malaria-in-an-area-of-an-unstable-seasonal-transmission-in-sudan
#11
Abdelrahim O Mohamed, Muzamil M Abdel Hamid, Omer S Mohamed, Nuha S Elkando, Abdelmaroof Suliman, Mariam A Adam, Fahad Awad Ali Elnour, Elfatih M Malik
BACKGROUND: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28400526/plasmodium-falciparum-k13-mutations-differentially-impact-ozonide-susceptibility-and-parasite-fitness-in-vitro
#12
Judith Straimer, Nina F Gnädig, Barbara H Stokes, Michelle Ehrenberger, Audrey A Crane, David A Fidock
The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based combination therapies (ACTs), underscore the urgent need to identify suitable replacement drugs. Discovery and development efforts have identified a series of ozonides with attractive chemical and pharmacological properties that are being touted as suitable replacements. Partial resistance to ART, defined as delayed parasite clearance in malaria patients treated with an ART derivative or an ACT, has been associated with mutations in the P...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28388902/therapeutic-efficacy-and-artemisinin-resistance-in-northern-myanmar-evidence-from-in-vivo-and-molecular-marker-studies
#13
Moe Kyaw Myint, Charlotte Rasmussen, Aung Thi, Dorina Bustos, Pascal Ringwald, Khin Lin
BACKGROUND: In Myanmar, three types of artemisinin-based combination therapy (ACT) are recommended as first-line treatment of uncomplicated falciparum malaria: artemether-lumefantrine (AL), artesunate-mefloquine (AS + MQ), and dihydroartemisinin-piperaquine (DP). Resistance to both artemisinins and ACT partner drugs has been reported from the Greater Mekong Sub-region, and regular efficacy monitoring of the recommended ACT is conducted in Myanmar. This paper reports on results from studies to monitor the efficacy of the three forms of ACT in sentinel sites in northern Myanmar, and investigations of mutations in the Kelch13 (k13) propeller domain...
April 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28372588/prolonged-parasite-clearance-in-a-chinese-splenectomized-patient-with-falciparum-malaria-imported-from-nigeria
#14
Hong-Wei Zhang, San-Jin Li, Tao Hu, Yong-Min Yu, Cheng-Yun Yang, Rui-Min Zhou, Ying Liu, Jing Tang, Jing-Jing Wang, Xiu-Yun Wang, Yong-Xiang Sun, Zhan-Chun Feng, Bian-Li Xu
BACKGROUND: The spleen plays a pivotal role in the rapid clearance of parasitized red blood cells in patients with falciparum malaria after artemisinin treatment. Prolonged parasite clearance can be found in patients who have had a splenectomy, or those with hemoglobin abnormalities and/or reduced immunity, which are all distinguishable from artemisinin resistance. This paper reports on a case of prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria...
April 4, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28358871/post-licensure-safety-evaluation-of-dihydroartemisinin-piperaquine-in-the-three-major-ecological-zones-across-ghana
#15
Abraham R Oduro, Seth Owusu-Agyei, Margaret Gyapong, Isaac Osei, Alex Adjei, Abena Yawson, Edward Sobe, Rita Baiden, Martin Adjuik, Fred Binka
BACKGROUND: Uncommon and rare adverse events (AEs), with delayed onset may not be detected before new drugs are licensed and deployed. The present study examined the post licensure safety of dihydroartemisinin-piperaquine (DHP) as an additional treatment for malaria in Ghana. The relationship between the incidence of AEs, treatment completion rate, participant characteristics and concomitant medications are reported. METHODS: A study conducted from September 2013 to June 2014 in Navrongo, Kintampo and Dodowa health research centres in Ghana is presented...
2017: PloS One
https://www.readbyqxmd.com/read/28329368/intermittent-preventive-treatment-with-dihydroartemisinin-piperaquine-for-the-prevention-of-malaria-among-hiv-infected-pregnant-women
#16
Paul Natureeba, Abel Kakuru, Mary Muhindo, Eric Littmann, Teddy Ochieng, John Ategeka, Catherine A Koss, Albert Plenty, Edwin D Charlebois, Tamara D Clark, Bridget Nzarubara, Miriam Nakalembe, Deborah Cohan, Gabrielle Rizzuto, Atis Muehlenbachs, Theodore Ruel, Prasanna Jagannathan, Diane V Havlir, Moses R Kamya, Grant Dorsey
Background.: Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide treated nets (ITNs) remain the main interventions for prevention of malaria in HIV-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these intervention and new ones are needed. Methods.: We conducted a double-blind randomized placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide (IRS) had recently been implemented...
February 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28322709/treatment-failure-of-dihydroartemisinin-piperaquine-for-plasmodium-falciparum-malaria-vietnam
#17
Bui Quang Phuc, Charlotte Rasmussen, Tran Thanh Duong, Le Than Dong, Mai Anh Loi, Didier Ménard, Joel Tarning, Dorina Bustos, Pascal Ringwald, Gawrie Loku Galappaththy, Nguyen Quang Thieu
We conducted a study in Binh Phuoc, Vietnam, in 2015 on the therapeutic efficacy of dihydroartemisinin/piperaquine for Plasmodium falciparum malaria. A high number of treatment failures (14/40) was found, and piperaquine resistance in Vietnam was confirmed. A change in the malaria treatment policy for Vietnam is in process.
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28302108/confirmation-of-plasmodium-falciparum-in-vitro-resistance-to-monodesethylamodiaquine-and-chloroquine-in-dakar-senegal-in-2015
#18
Silman Diawara, Marylin Madamet, Mame Bou Kounta, Gora Lo, Khalifa Ababacar Wade, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
BACKGROUND: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28261759/dihydroartemisinin-sensitizes-human-lung-adenocarcinoma-a549-cells-to-arsenic-trioxide-via-apoptosis
#19
Hongyu Chen, Shiyan Gu, Huangmei Dai, Xinyang Li, Zunzhen Zhang
Recent studies have shown that arsenic trioxide (ATO) is an effective anti-cancer drug for treatment of acute promyelocytic leukemia and other types of human cancer. However, we have found that lung cancer cells constantly develop a high level of resistance to ATO. In this study, we have explored a possibility of combination of dihydroartemisinin (DHA) and ATO treatments to reduce ATO resistance of lung cancer cells. We determined the combinatory effects of DHA and ATO on cytotoxicity of human lung adenocarcinoma (A549) cells...
March 6, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28259625/characterization-of-the-selective-alkylation-site-in-hemoglobin-a-by-dihydroartemisinin-with-tandem-mass-spectrometry
#20
Khomsan Tiensomjitr, Samran Prabpai, Palangpon Kongsaeree
The reaction between the antimalarial drug dihydroartemisinin (DHA) and hemoglobin A (HbA) was investigated in vitro. A fluorescein-tagged artemisinin analog reacted with HbA and fluorescent HbA-drug adducts could be visualized on SDS-PAGE to confirm stable covalent reaction adducts and necessity of the endoperoxide moiety and Fe(II). Mass spectrometric analyses revealed that DHA favourably alkylated protein part rather than heme and the modification site was identified to be at Tyr35 of the beta globin chain...
June 2017: International Journal of Biological Macromolecules
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