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https://www.readbyqxmd.com/read/28076793/chloroquine-inducible-par-4-secretion-is-essential-for-tumor-cell-apoptosis-and-inhibition-of-metastasis
#1
Ravshan Burikhanov, Nikhil Hebbar, Sunil K Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S Watt, Danny R Welch, Jodi Maranchie, Akihiro Harada, Vivek M Rangnekar
The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28036313/pretreatment-elevated-erythrocyte-sedimentation-rate-and-c-reactive-protein-as-a-predictor-of-malarial-complications
#2
Sachin Vemula, Vidyalakshmi Katara, Unnikrishnan Bhaskaran, Sushma Adappa, Mahabala Chakrapani
INTRODUCTION: Complications of malaria can develop suddenly and unexpectedly. Although various parameters have been associated with severity of malaria, they have not been studied as predictors of these events. Many of the malarial complications are inflammatory in nature, and C-reactive protein (CRP) and elevated erythrocyte sedimentation rate (ESR) could be early markers of these complications and might precede and predict the development of complications. METHODOLOGY: A total of 122 inpatients with uncomplicated newly diagnosed malaria were studied...
December 30, 2016: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/28031457/force-spectroscopy-of-the-plasmodium-falciparum-vaccine-candidate-circumsporozoite-protein-suggests-a-mechanically-pliable-repeat-region
#3
Aditya Prasad Patra, Shobhona Sharma, Sri Rama Koti Ainavarapu
The most effective vaccine candidate of malaria is based on the Plasmodium falciparum circumsporozoite protein (CSP), a major surface protein implicated in the structural strength, motility and immune evasion properties of the infective sporozoites. It is suspected that reversible conformational changes of CSP are required for infection of the mammalian host, but CSP's detailed structure and dynamic properties remain incompletely understood, limiting our understanding of its function in the infection. Here, we report the structural and mechanical properties of the CSP studied using single-molecule force spectroscopy on several constructs, one including CSP's central region rich in NANP amino acid repeats (CSPrep) and a second consisting of a near full-length sequence without the signal and anchor hydrophobic domains (CSPΔHP)...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28012440/nrf2-inhibition-reverses-the-resistance-of-cisplatin-resistant-head-and-neck-cancer-cells-to-artesunate-induced-ferroptosis
#4
Jong-Lyel Roh, Eun Hye Kim, Hyejin Jang, Daiha Shin
: Artesunate, an anti-malarial drug, has been repurposed as an anticancer drug due to its induction of cell death via reactive oxygen species (ROS) production. However, the molecular mechanisms regulating cancer cell death and the resistance of cells to artesunate remain unclear. We investigated the molecular mechanisms behind the antitumor effects of artesunate and an approach to overcome artesunate resistance in head and neck cancer (HNC). The effects of artesunate and trigonelline were tested in different HNC cell lines, including three cisplatin-resistant HNC cell lines...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28000518/artemisinin-inhibits-inflammatory-response-via-regulating-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#5
Ke Si Wang, Junbo Li, Zhe Wang, Chunliu Mi, Juan Ma, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Xuejun Jin
Artemisinin, isolated from the Chinese plant Artemisia annua, has been used for many years to treat different forms of malarial parasites. In this study, we explored the anti-inflammatory activity of artemisinin and the underlying mechanism of this action. We demonstrated that the anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice. Then the artemisinin significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. Artemisinin also inhibited TNF-α induced phosphorylation and degradation of IκBα, p65 nuclear translocation...
December 21, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27941926/dihydroartemisinin-inhibits-catabolism-in-rat-chondrocytes-by-activating-autophagy-via-inhibition-of-the-nf-%C3%AE%C2%BAb-pathway
#6
Li-Bo Jiang, De-Hua Meng, Soo-Min Lee, Shu-Hao Liu, Qin-Tong Xu, Yang Wang, Jian Zhang
Osteoarthritis is a disease with inflammatory and catabolic imbalance in cartilage. Dihydroartemisinin (DHA), a natural and safe anti-malarial agent, has been reported to inhibit inflammation, but its effects on chondrocytes have yet to be elucidated. We investigated the effects of DHA on catabolism in chondrocytes. Viability of SD rats chondrocytes was analyzed. Autophagy levels were determined via expression of autophagic markers LC3 and ATG5, GFP-LC3 analysis, acridine orange staining, and electron microscopy...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936446/design-synthesis-and-evaluation-of-4-aminoquinoline-purine-hybrids-as-potential-antiplasmodial-agents
#7
P Linga Reddy, Shabana I Khan, Prija Ponnan, Mohit Tripathi, Diwan S Rawat
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P...
December 1, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27923179/structural-dynamics-of-casein-kinase-i-cki-from-malarial-parasite-plasmodium-falciparum-isolate-3d7-insights-from-theoretical-modelling-and-molecular-simulations
#8
Budheswar Dehury, Santosh Kumar Behera, Namita Mahapatra
The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation...
January 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#9
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#10
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27873143/regulation-of-rac1-gtpase-activity-by-quinine-through-g-protein-and-bitter-taste-receptor-t2r4
#11
Crystal Sidhu, Appalaraju Jaggupilli, Prashen Chelikani, Rajinder P Bhullar
Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton reorganization. T2R4 is a bitter taste receptor belonging to the G protein-coupled receptor family of proteins. In addition to mediating bitter taste perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal epithelium, airways, brain, testis suggesting a much broader physiological function for these receptors. Anti-malarial drug and a bitter tasting compound, quinine, is a known agonist for T2R4, whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist...
November 22, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27814577/identification-of-natural-peptides-as-a-new-class-of-antimalarial-drugs-by-in-silico-approaches
#12
Ramar Perumal Samy, Sok Lin Foo, Octavio L Franco, Bradley G Stiles, Alan P Kumar, Gautam Sethi, Lina Hk Lim
Malaria is one of the most widespread and serious parasitic diseases worldwide. Currently available antimalarial drugs have side effects, and many strains of Plasmodia have developed resistance to such drugs. The present review examines the use of annexins and of natural peptides from snake venom as a new class of anti-malarial agents, with the key property of reducing inflammation. Severe cases of malaria manifest elevated serum levels of liver enzymes, inflammation, fibrin deposition, apoptosis, and reduction in peripheral CD8(+) T cells...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27806730/comparative-physiological-plasticity-to-desiccation-in-distinct-populations-of-the-malarial-mosquito-anopheles-coluzzii
#13
K Hidalgo, D Siaussat, V Braman, K R Dabiré, F Simard, K Mouline, D Renault
BACKGROUND: In West Africa, populations of the malaria vector mosquito, Anopheles coluzzii, are seasonally exposed to strong desiccating conditions during the dry season. Their dynamics strictly follows the pace of the availability of suitable larval development sites (water collections). Accordingly, mosquitoes can reproduce all year long where permanent breeding is possible, or stop reproduction and virtually disappear at the onset of the dry season when surface water dries up, like observed in temporary habitats of dry savannah areas...
November 2, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27806725/the-effect-of-malaria-and-anti-malarial-drugs-on-skeletal-and-cardiac-muscles
#14
REVIEW
Mauro Toledo Marrelli, Marco Brotto
Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles...
November 2, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27799332/ph-alkalinization-by-chloroquine-suppresses-pathogenic-burkholderia-type-6-secretion-system-1-and-multinucleated-giant-cells
#15
Jennifer Chua, Jeffrey L Senft, Stephen J Lockett, Paul J Brett, Mary N Burtnick, David DeShazer, Arthur M Friedlander
Burkholderia mallei and B. pseudomallei cause glanders and melioidosis, respectively, in humans and animals. A hallmark of pathogenesis is the formation of granulomas containing multinucleated giant cells (MNGCs) and cell death. These processes depend on type 6 secretion system 1 (T6SS-1), which is required for virulence in animals. We examined the cell biology of MNGC formation and cell death. We found that chloroquine diphosphate (CLQ), an antimalarial drug, inhibits Burkholderia growth, phagosomal escape, and subsequent MNGC formation...
January 2017: Infection and Immunity
https://www.readbyqxmd.com/read/27793909/attenuation-of-colchicine-toxicity-in-drug-resistant-cancer-cells-by-co-treatment-with-anti-malarial-drugs
#16
Ae-Ran Choi, Ju-Hwa Kim, Ji Hyun Cheon, Hyung Sik Kim, Sungpil Yoon
BACKGROUND/AIM: Colchicine (COL) is a well-known and potent microtubule targeting anticancer agent. The purpose of our study was to identify conditions that increase sensitization of COL-resistant cancer cells that overexpress P-glycoprotein (P-gp). MATERIALS AND METHODS: The anti-malarial drugs chloroquine (CHL), mefloquine (MEF) and primaquine (PRI) have been shown to increase sensitization in drug-resistant KBV20C cells via P-gp inhibition. Therefore, we tested whether co-treatment of COL with PRI, CHL or MEF increases sensitivity in COL-resistant KBV20C cells over that of cells treated with COL alone and whether these effects are attributable to P-gp activity...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27788475/the-pharmacological-stimulation-of-nurr1-improves-cognitive-functions-via-enhancement-of-adult-hippocampal-neurogenesis
#17
Jin-Il Kim, Seong Gak Jeon, Kyoung Ah Kim, Yong Jun Kim, Eun Ji Song, Junghyun Choi, Kyu Jeung Ahn, Chong-Jin Kim, Ho Yeon Chung, Minho Moon, Hyunju Chung
The nuclear receptor related-1 (Nurr1) protein plays an important role in both the development of neural precursor cells (NPCs) and cognitive functions. Despite its relevance, the effects of Nurr1 on adult hippocampal neurogenesis have not been thoroughly investigated. Here we used RT-PCR, western blot, and immunocytochemistry to show that adult hippocampal NPCs abundantly express Nurr1. We then examined the effect of Nurr1 activation on adult hippocampal NPCs using amodiaquine (AQ), an anti-malarial drug that was recently discovered to be a Nurr1 agonist...
November 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27773616/compartmentalized-metabolic-engineering-for-artemisinin-biosynthesis-and-effective-malaria-treatment-by-oral-delivery-of-plant-cells
#18
Karan Malhotra, Mayavan Subramaniyan, Khushboo Rawat, Md Kalamuddin, M Irfan Qureshi, Pawan Malhotra, Asif Mohmmed, Katrina Cornish, Henry Daniell, Shashi Kumar
Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills >500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized (∼0...
November 7, 2016: Molecular Plant
https://www.readbyqxmd.com/read/27769430/simultaneous-capture-and-sequential-detection-of-two-malarial-biomarkers-on-magnetic-microparticles
#19
Christine F Markwalter, Keersten M Ricks, Anna L Bitting, Lwiindi Mudenda, David W Wright
We have developed a rapid magnetic microparticle-based detection strategy for malarial biomarkers Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein II (PfHRPII). In this assay, magnetic particles functionalized with antibodies specific for pLDH and PfHRPII as well as detection antibodies with distinct enzymes for each biomarker are added to parasitized lysed blood samples. Sandwich complexes for pLDH and PfHRPII form on the surface of the magnetic beads, which are washed and sequentially re-suspended in detection enzyme substrate for each antigen...
December 1, 2016: Talanta
https://www.readbyqxmd.com/read/27738107/disrupting-the-allosteric-interaction-between-the-plasmodium-falciparum-camp-dependent-kinase-and-its-regulatory-subunit
#20
Dene R Littler, Hayley E Bullen, Katherine L Harvey, Travis Beddoe, Brendan S Crabb, Jamie Rossjohn, Paul R Gilson
The ubiquitous second messenger cAMP mediates signal transduction processes in the malarial parasite that regulate host erythrocyte invasion and the proliferation of merozoites. In Plasmodium falciparum, the central receptor for cAMP is the single regulatory subunit (R) of protein kinase A (PKA). To aid the development of compounds that can selectively dysregulate parasite PKA signaling, we solved the structure of the PKA regulatory subunit in complex with cAMP and a related analogue that displays antimalarial activity, (Sp)-2-Cl-cAMPS...
December 2, 2016: Journal of Biological Chemistry
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