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Jia-Tian Cao, Hui-Min Mo, Yue Wang, Kai Zhao, Tian-Tian Zhang, Chang-Qian Wang, Kai-Lin Xu, Zhi-Hua Han
Dihydroartemisinin (DHA) is a derivative of artemisinin. The present study aimed to investigate whether DHA induces apoptosis in the THP-1 human acute monocytic leukemia cell line (AMoL), and to identify the relative molecular mechanisms. The results of the present study demonstrated that the viability of THP-1 cells were inhibited by DHA in a dose- and time-dependent manner, which was accompanied by morphological characteristics associated with apoptosis. After 24 h of 200 µM DHA treatment, the proportion of apoptotic cells was significantly increased compared with the untreated controls (P<0...
March 2018: Oncology Letters
Yong Wang, Xiaoyuan Xu, Xiaojian Wu, Weibin Chen, Fangmei Huang, Xiaomin Gui
The aim of the present study was to investigate the effect of dihydroartemisinin (DHA) on a multiple myeloma cell line. An MTT assay, flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) were used for the analysis of cell viability, cell cycle distribution and c-Jun N-terminal kinase (JNK) expression, respectively. Treatment of U266 cells using DHA caused a significant (P<0.05) decrease in cell viability compared with the control cells. An increase in the concentration of DHA from 1 to 100 µmol/l reduced cell viability from 87 to 35% compared with 100% in the control cultures at 48 h...
February 2018: Oncology Letters
Dongsheng Wang, Bei Zhong, Yu Li, Xiaodong Liu
As a derivative of artemisinin, dihydroartemisinin is effective in the treatment of malaria. Dihydroartemisinin has been identified to possess inhibitory effects in numerous types of animal model with tumors, indicating that it has an antineoplastic effect. The aim of the present study was to analyze the potential anticancer effects of dihydroartemisinin, particularly its effect on apoptosis of colon cancer cells. In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B-cell lymphoma-2-associated X-protein expression, increased caspase-3/9 activities, decreased poly(ADP-ribose) polymerase levels, decreased phosphorylation of extracellular-signal-regulated kinase, and increased phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in colon cancer cells...
February 2018: Oncology Letters
Anne Perisse, Guillaume Velut, Emilie Javelle, Gwion Loarer, Remy Michel, F Simon
Background: Malaria prevention and treatment are big challenges for the French forces deployed in sub-Saharan Africa. Since December 2013, 1,800 French soldiers have been deployed at any one time in the Central African Republic in the framework of "Operation Sangaris" and European Union Force (EUFOR). Over the 2014-2015 period, about 500 cases of malaria were notified in these troops during the operation or after their return (annual incidence: 13.4 p.100 person-year). The recommendation to use dihydroartemisinin-piperaquine (DHA-PQ) as the first-line treatment for French soldiers suffering from uncomplicated Plasmodium falciparum malaria in endemic areas is not always followed in practice in the field by French military general practitioners (GPs)...
February 7, 2018: Military Medicine
Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John Bradley, Koualy Sanogo, Daouda T Kone, Kalifa Diarra, Sekouba Keita, Djibrilla Issiaka, Sekou F Traore, Charles McCulloch, Will J R Stone, Jimee Hwang, Olaf Müller, Joelle M Brown, Vinay Srinivasan, Chris Drakeley, Roly Gosling, Ingrid Chen, Teun Bousema
BACKGROUND: Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. METHODS: This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali)...
February 5, 2018: Lancet Infectious Diseases
Xiang Li, Yue Gao, Qiang Zhang, Nan Hu, Dong Han, Shangwei Ning, Zhuo Ao
Chronic myelocytic leukemia (CML) is characterized by increased and unregulated growth of predominantly myeloid cells in the bone marrow, and accumulation of these cells in blood. We investigated the effects of an anti-malarial drug, dihydroartemisinin (DHA), on K562 CML cells. We identified 34 mRNAs and eight lncRNAs dysregulated following DHA treatment in pure and hemin-induced K562 cells. Up- or downregulation of these potential DHA targets increased with increasing DHA concentration. We also constructed and analyzed a DHA-related mRNA-lncRNA regulation network in K562 cells, and found that four DHA-modulated mRNAs regulated by four lncRNAs participated in the steroid biosynthesis pathway...
January 5, 2018: Oncotarget
Roberto Amato, Richard D Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick M Fairhurst, Dominic P Kwiatkowski
BACKGROUND: Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin-piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. METHODS: We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013...
February 1, 2018: Lancet Infectious Diseases
Meghna Desai, Jenny Hill, Silke Fernandes, Patrick Walker, Christopher Pell, Julie Gutman, Kassoum Kayentao, Raquel Gonzalez, Jayne Webster, Brian Greenwood, Michel Cot, Feiko O Ter Kuile
Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012...
January 30, 2018: Lancet Infectious Diseases
John F Deeken, Hongkun Wang, Marion Hartley, Amrita K Cheema, Brandon Smaglo, Jimmy J Hwang, Aiwu Ruth He, Louis M Weiner, John L Marshall, Giuseppe Giaccone, Stephen Liu, Jim Luecht, Jay Y Spiegel, Michael J Pishvaian
PURPOSE: The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models. Proposed anti-cancer mechanisms include DNA damage, inhibition of angiogenesis, TRAIL-mediated apoptosis, and inhibition of signaling pathways. We performed a phase I study to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenous artesunate (IV AS). METHODS: Patients were enrolled in an accelerated titration dose escalation study with planned dose levels of 8, 12, 18, 25, 34 and 45 mg/kg given on days 1 and 8 of a 21-day cycle...
February 1, 2018: Cancer Chemotherapy and Pharmacology
Huijuan Liu, Qin Tian, Xiaoyu Ai, Yuan Qin, Zhanhong Cui, Meng Li, Jiahuan Yang, Denghui Zhai, Yanrong Liu, Shuang Chen, Jing Meng, Tao Sun, Honggang Zhou, Cheng Yang
Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo. Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice...
December 29, 2017: Oncotarget
Rui-Jun Ju, Lan Cheng, Xiao-Ming Peng, Teng Wang, Cui-Qing Li, Xiao-Li Song, Shuang Liu, Jian-Ping Chao, Xue-Tao Li
Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin...
January 30, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Francesco Grandesso, Ousmane Guindo, Lynda Woi Messe, Rockyath Makarimi, Aliou Traore, Souleymane Dama, Ibrahim Maman Laminou, Jean Rigal, Martin de Smet, Odile Ouwe Missi Oukem-Boyer, Ogobara K Doumbo, Abdoulaye Djimdé, Jean-François Etard
BACKGROUND: Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality. METHODS: A WHO standard protocol was used to assess efficacy of the combinations artesunate-amodiaquine (AS-AQ Winthrop®), dihydroartemisinin-piperaquine (DHA-PPQ, Eurartesim®) and artemether-lumefantrine (AM-LM, Coartem®) taken under supervision and respecting pharmaceutical recommendations...
January 25, 2018: Malaria Journal
Xiaohui Yan, Pengfei Li, Yihong Zhan, Miao Qi, Jin Liu, Zhifeng An, Weiwei Yang, Hui Xiao, Hongmei Wu, Yitao Qi, Huanjie Shao
Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. A significant fraction of NSCLC carries activating mutations in epidermal growth factor receptor (EGFR) or RAS oncogene. Dihydroartemisinin (DHA) is a semisynthetic derivative of the herbal antimalarial drug artemisinin that has been recently reported to exhibit anti-cancer activity. To develop new therapeutic strategies for NSCLC, we investigated the interactions between DHA and ABT-263 in NSCLC cells harboring EGFR or RAS mutation...
January 19, 2018: Biochemical Pharmacology
Zuowang Cheng, Ruixia Qi, Liqun Li, Qiang Liu, Wenqian Zhang, Xia Zhou, Dongmei Xu, Thaddeus D Allen, Silin Pan, Ju Liu
Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jeanne Rini Poespoprodjo, Enny Kenangalem, Johny Wafom, Freis Chandrawati, Agatha M Puspitasari, Benedikt Ley, Leily Trianti, Zoé Korten, Asik Surya, Din Syafruddin, Nicholas M Anstey, Jutta Marfurt, Rintis Noviyanti, Ric N Price
Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days...
January 15, 2018: American Journal of Tropical Medicine and Hygiene
Serena De Lucia, Ioannis Tsamesidis, Maria Carmina Pau, Kristina R Kesely, Antonella Pantaleo, Francesco Turrini
Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P...
2018: PloS One
Jingwei Huang, Kang Xiong, Houshuang Zhang, Yanzhen Zhao, Jie Cao, Haiyan Gong, Yongzhi Zhou, Jinlin Zhou
BACKGROUND: Human babesiosis is an infectious disease that is epidemic in various regions all over the world. The predominant causative pathogen of this disease is the intra-erythrocytic parasite Babesia microti. The thioredoxin system is one of the major weapons that is used in the resistance to the reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by host immune system. In other intra-erythrocytic apicomplexans like the malaria parasite Plasmodium falciparum, anti-oxidative proteins are promising targets for the development of anti-parasitic drugs...
January 15, 2018: Parasites & Vectors
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
Gab-Man Park, Hyun Park, Sangtae Oh, Seokjoon Lee
We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate...
December 2017: Korean Journal of Parasitology
Olusola Ojurongbe, Christian N Nguetse, Samuel A Fayemiwo, Catherine O Falade, Taiwo A Ojurongbe, Bolaji N Thomas, Christian G Meyer, Thirumalaisamy P Velavan
This study assesses the prevalence of asymptomatic Plasmodium falciparum parasitemia positivity and P. falciparum dihydrofolate reductase (pfdhfr) mutations in parasite isolates among pregnant women in Southwest Nigeria. Plasmodium falciparum parasitemia was confirmed by microscopy and nested PCR in 200 pregnant women attending antenatal care. The prevalence of pfdhfr polymorphisms was determined by direct sequencing of the gene fragments containing the C50R, N51I, C59R, S108N, and I164L mutations. Information on the use of antimalarial drugs and methods applied to prevent malaria were obtained by a questionnaire...
January 10, 2018: Pathogens and Global Health
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