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https://www.readbyqxmd.com/read/28732068/effects-of-liver-stage-clearance-by-primaquine-on-gametocyte-carriage-of-plasmodium-vivax-and-p-falciparum
#1
Rahel Wampfler, Natalie E Hofmann, Stephan Karl, Inoni Betuela, Benson Kinboro, Lina Lorry, Mariabeth Silkey, Leanne J Robinson, Ivo Mueller, Ingrid Felger
BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses. METHODS: Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo...
July 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28729403/autophagy-inhibition-improves-sunitinib-efficacy-in-pancreatic-neuroendocrine-tumors-via-a-lysosome-dependent-mechanism
#2
Tabea Wiedmer, Annika Blank, Sophia Pantasis, Lea Normand, Ruben Bill, Philippe Krebs, Mario P Tschan, Ilaria Marinoni, Aurel Perren
Increasing the efficacy of approved systemic treatments in metastasized pancreatic neuroendocrine tumors (PanNETs) is an unmet medical need. The anti-angiogenic tyrosine kinase inhibitor sunitinib is approved for PanNET treatment. Additionally, sunitinib is a lysosomotropic drug and such drugs can induce lysosomal membrane permeabilization as well as autophagy. We investigated sunitinib-induced autophagy as a possible mechanism of PanNET therapy resistance. Sunitinib accumulated in lysosomes and induced autophagy in PanNET cell lines...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#3
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726776/autophagosome-maturation-mediated-by-rab7-contributes-to-neuroprotection-of-hypoxic-preconditioning-against-global-cerebral-ischemia-in-rats
#4
Lixuan Zhan, Siyuan Chen, Kongping Li, Donghai Liang, Xinyong Zhu, Liu Liu, Zhiwei Lu, Weiwen Sun, En Xu
Autophagy disruption leads to neuronal damage in hypoxic-ischemic brain injury. Rab7, a member of the Rab GTPase superfamily, has a unique role in the regulation of autophagy. Hypoxic preconditioning (HPC) provides neuroprotection against transient global cerebral ischemia (tGCI). However, the underlying mechanisms remain poorly understood. Thus, the current study explored the potential molecular mechanism of the neuroprotective effect of HPC by investigating how Rab7 mediates autophagosome (AP) maturation after tGCI in adult rats...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#5
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28717157/cellular-uptake-pathways-of-sepiolite-nanofibers-and-dna-transfection-improvement
#6
Fidel Antonio Castro-Smirnov, Jeanne Ayache, Jean-Rémi Bertrand, Elodie Dardillac, Eric Le Cam, Olivier Piétrement, Pilar Aranda, Eduardo Ruiz-Hitzky, Bernard S Lopez
Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier because it can be naturally internalized into mammalian cells, due to its nano-size dimension. Therefore, deciphering the mechanisms of sepiolite cell internalization constitutes a question interesting biotechnology, for the use of sepiolite as nanocarrier, as well as environmental and public health concerns. Though it is low, the perfectly stable and natural intrinsic fluorescence of sepiolite nanofibers allows to follow their fate into cells by specifically sensitive technics...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716028/antiplasmodial-potential-and-quantification-of-aloin-and-aloe-emodin-in-aloe-vera-collected-from-different-climatic-regions-of-india
#7
Sandeep Kumar, Manila Yadav, Amita Yadav, Pooja Rohilla, Jaya Parkash Yadav
BACKGROUND: In this study, Aloe vera samples were collected from different climatic regions of India. Quantitative HPTLC (high performance thin layer chromatography) analysis of important anthraquinones aloin and aloe-emodin and antiplasmodial activity of crude aqueous extracts was done to estimate the effects of these constituents on antiplasmodial potential of the plant. METHODS: HPTLC system equipped with a sample applicator Linomat V with CAMAG sample syringe, twin rough plate development chamber (20 x 10 cm), TLC Scanner 3 and integration software WINCATS 1...
July 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28714338/antiplasmodial-prenylated-flavanonols-from-tephrosia-subtriflora
#8
Lois M Muiva-Mutisya, Yoseph Atilaw, Matthias Heydenreich, Andreas Koch, Hoseah M Akala, Agnes C Cheruiyot, Matthew L Brown, Beatrice Irungu, Faith A Okalebo, Solomon Derese, Charles Mutai, Abiy Yenesew
The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1...
July 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28713934/upregulation-of-connexin-43-and-apoptosis%C3%A2-associated-protein-expression-by-high-glucose-in-h9c2-cells-was-improved-by-resveratrol-via-the-autophagy-signaling-pathway
#9
Guang-Yu Wang, Ya-Guang Bi, Xiang-Dong Liu, Jun-Feng Han, Meng Wei, Qing-Yong Zhang
The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713884/antimicrobial-activity-of-organometallic-isonicotinyl-and-pyrazinyl-ferrocenyl-derived-complexes
#10
Tameryn Stringer, Ronnett Seldon, Nicole Liu, Digby F Warner, Christina Tam, Luisa W Cheng, Kirkwood M Land, Peter J Smith, Kelly Chibale, Gregory S Smith
Isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. Three heterobimetallic complexes were also synthesized from the Schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. All complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. Against Mycobacterium tuberculosis H37Rv, the platinum group metal complexes showed glycerol-dependent antimycobacterial activity...
July 17, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28708385/chloroquine-modified-hydroxyethyl-starch-as-a-polymeric-drug-for-cancer-therapy
#11
Richard Sleightholm, Bin Yang, Fei Yu, Ying Xie, David Oupický
Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. Atomic force microscopy was used to demonstrate a pH-dependent assembly of CQ-HES into well-defined nanoparticles...
July 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#12
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28706336/palmoplantar-exfoliation-due-to-chloroquine
#13
Pragya Ashok Nair, Trusha Patel
Chloroquine is the drug very frequently used for the treatment of malaria. It is also used in amebiasis, rheumatoid arthritis, and various dermatological conditions. Chloroquine can cause muscle problems, loss of appetite, and diarrhea as a side effect. Cutaneous toxicity includes pruritus, hair loss, photosensitivity, and color changes. Exfoliation of skin over palms and soles is caused by chemotherapeutic drugs such as axitinib, fluorouracil, idarubicin, doxorubicin, sunitinib, sorafenib, and paclitaxel. Here, a case of a 40-year-old female is presented who developed palmoplantar exfoliation with depigmentation after taking chloroquine...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28706237/suppressed-autophagic-response-underlies-augmentation-of-renal-ischemia-reperfusion-injury-by-type-2-diabetes
#14
Shingo Muratsubaki, Atsushi Kuno, Masaya Tanno, Takayuki Miki, Toshiyuki Yano, Hirohito Sugawara, Satoru Shibata, Koki Abe, Satoko Ishikawa, Kouhei Ohno, Yukishige Kimura, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Masashi Mizuno, Tetsuji Miura
Diabetes mellitus is a major risk factor for acute kidney injury (AKI). Here, we hypothesized that suppression of autophagic response underlies aggravation of renal ischemia/reperfusion (I/R) injury by type 2 diabetes mellitus (T2DM). In OLETF, a rat model of T2DM, and its non-diabetic control, LETO, AKI was induced by unilateral nephrectomy and 30-min occlusion and 24-h reperfusion of the renal artery in the contralateral kidney. Levels of serum creatinine and blood urea nitrogen and tubular injury score after I/R were significantly higher in OLETF than in LETO...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#15
Derong Cui, Dawei Sun, Xintao Wang, Liye Yi, Ewa Kulikowicz, Michael Reyes, Junchao Zhu, Zeng-Jin Yang, Wei Jiang, Raymond C Koehler
To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703297/neither-eosinophils-nor-neutrophils-require-atg5-dependent-autophagy-for-extracellular-dna-trap-formation
#16
Nina Germic, Darko Stojkov, Kevin Oberson, Shida Yousefi, Hans-Uwe Simon
The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28702931/autophagy-induced-by-bovine-viral-diarrhea-virus-infection-counteracts-apoptosis-and-innate-immune-activation
#17
Yulong Zhou, Yachao Ren, Yanlong Cong, Yu Mu, Renfu Yin, Zhuang Ding
Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP) and cytopathic (CP). One strategy that has been used to treat or prevent virus-associated diseases is the modulation of autophagy, which is used by the innate immune system to defend against viral infection; however, at present, the interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B) with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient MDBKs (shBCN1-MDBK cells) were constructed...
July 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28693552/chloroquine-efficacy-for-plasmodium-vivax-in-myanmar-in-populations-with-high-genetic-diversity-and-moderate-parasite-gene-flow
#18
Myo Win Htun, Nan Cho Nwe Mon, Khin Myo Aye, Chan Myae Hlaing, Myat Phone Kyaw, Irene Handayuni, Hidayat Trimarsanto, Dorina Bustos, Pascal Ringwald, Ric N Price, Sarah Auburn, Kamala Thriemer
BACKGROUND: Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts. METHODS: Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28...
July 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28692943/progressive-increase-in-point-mutations-associates-chloroquine-resistance-even-after-withdrawal-of-chloroquine-use-in-india
#19
Sabyasachi Das, Satyajit Tripathy, Sourav Chattopadhayay, Balaram Das, Santanu Kar Mahapatra, Amiya Kumar Hati, Somenath Roy
Chloroquine (CQ) is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P...
June 29, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28689867/ex-vivo-activity-of-proveblue-a-methylene-blue-against-field-isolates-of-plasmodium-falciparum-in-dakar-senegal-from-2013-2015
#20
Bécaye Fall, Marylin Madamet, Silman Diawara, Sébastien Briolant, Khalifa Ababacar Wade, Gora Lo, Aminata Nakoulima, Mansour Fall, Raymond Bercion, Mame Bou Kounta, Rémi Amalvict, Nicolas Benoit, Mamadou Wague Gueye, Bakary Diatta, Boubacar Wade, Bruno Pradines
Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs...
July 6, 2017: International Journal of Antimicrobial Agents
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