@article {47500,
	title = {Conserved RNA binding activity of phosphatidyl inositol 5-phosphate 4-kinase (PIP4K2A)},
	journal = {Frontiers in Molecular Biosciences},
	volume = {8},
	year = {2021},
	month = {MAY},
	pages = {631281},
	type = {Article},
	abstract = {Plasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. During its life cycle, the malarial parasite Plasmodium goes through different asexual and sexual stages, in humans and mosquitoes. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In the case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that posttranscriptional regulation plays an important role in stage-specific gene expression. Translation repression of specific set of mRNA has been reported in gametocyte stages of the parasite. A conserved element present in the 3 {\textquoteleft} UTR of some of these transcripts was identified. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K2A) was identified as the protein that associates with these RNA. We now show that the RNA binding activity of PIP4K2A is independent of its kinase activity. We also observe that PIP4K2A is imported into the parasite from the host on Plasmodium berghei and Toxoplasma gondii. The RNA binding activity of PIP4K2A seems to be conserved across species from Drosophila and C. elegans to humans, suggesting that the RNA binding activity of PIP4K may be important, and there may be host transcripts that may be regulated by PIP4K2A. These results identify a novel RNA binding role for PIP4K2A that may not only play a role in Plasmodium propagation but may also function in regulating gene expression in multicellular organisms.},
	keywords = {malaria, posttranscriptional gene regulation, RNA-protein interaction, translation regulation},
	doi = {10.3389/fmolb.2021.631281},
	author = {Behari, Jatin and Borkar, Pranita and Vindu, Arya and Dandewad, Vishal and Upadrasta, Sindhuri and Shanmugam, Dhanasekaran and Seshadri, Vasudevan}
}
@article {48375,
	title = {Profiling of metabolic alterations in mice infected with malaria parasites via high-resolution metabolomics},
	journal = {Molecular and Biochemical Parasitology},
	volume = {252},
	year = {2022},
	month = {NOV},
	pages = {111525},
	type = {Article},
	abstract = {<p>
	Background: Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood. Methods: In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA). Results: We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase. Conclusions: We have identified candidate marker metabolites that may be of relevance in the context of human malaria.</p>
},
	keywords = {Host response, Infectious diseases, malaria, metabolite, Plasmodium},
	issn = {0166-6851},
	doi = {10.1016/j.molbiopara.2022.111525},
	author = {Chhibber-Goel, Jyoti and Shukla, Anurag and Shanmugam, Dhanasekaran and Sharma, Amit}
}
@article {48993,
	title = {Antimalarial activity of anacardium occidentale leaf extracts against plasmodium falciparum transketolase (PfTK)},
	journal = {Acta Parasitologica},
	volume = {68},
	year = {2023},
	month = {DEC},
	pages = {832-841},
	type = {Article},
	abstract = {<p>
	BackgroundAs per estimates by WHO in 2021 almost half of the world{\textquoteright}s population was at risk of malaria and \&gt; 0.6 million deaths were attributed to malaria. Therefore, the present study was aimed to explore the antimalarial activity of extracts derived from the leaves of the plant Anacardium occidentale L., which has been used traditionally for the treatment of malaria. Different extracts of A.occidentale leaves were prepared and tested for their inhibitory activity against recombinant P. falciparum transketolase (rPfTK) enzyme, in vitro. Further, growth inhibitory activity against cultivated blood stage P. falciparum parasites (3D7 strain), was studied using SYBR Green fluorescence-based in vitro assays. Acute toxicity of the hydro alcoholic extracts of leaves of A. occidentale (HELA) at different concentrations was evaluated on mice and Zebra fish embryos. HELA showed 75.45 +/- 0.35\% inhibitory activity against the recombinant PfTk and 99.31 +/- 0.08\% growth inhibition against intra-erythrocytic stages of P. falciparum at the maximum concentration (50 mu g/ml) with IC50 of 4.17 +/- 0.22 mu g/ml. The toxicity test results showed that the heartbeat, somite formation, tail detachment and hatching of embryos were not affected when Zebra fish embryos were treated with 0.1 to 10 mu g/ml of the extract. However, at higher concentrations of the extract, at 48 h (1000 mu g/ml) and 96 h (100 mu g/ml and 1000 mu g/ml, respectively) there was no heartbeat in the fish embryos. In the acute oral toxicity tests performed on mice, the extract showed no toxicity up to 300 mg/kg body weight in mice.ConclusionThe hydro-alcoholic extract of leaves of A. occidentale L. showed potent antimalarial activity against blood stage P. falciparum. Based on the observed inhibitory activity on the transketolase enzyme of P. falciparum it is likely that this enzyme is the target for the development of bioactive molecules present in the plant extracts. The promising anti-malarial activity of purified compounds from leaves of A. occidentale needs to be further explored for development of new anti-malarial therapy.</p>
},
	keywords = {Anacardium occidentale L, Antimalarial activity, malaria, Plasmodium falciparum, Transketolase},
	issn = {1230-2821},
	doi = {10.1007/s11686-023-00718-6},
	author = {Kaushik, Meenakshi and Hoti, Sugeerappa L. and Saxena, Jitendra Kumar and Hingamire, Tejashri and Shanmugam, Dhanasekaran and Joshi, Rajesh K. and Metgud, Sharada C. and Ungar, Banappa and Singh, Ishwar and Hegde, Harsha V.}
}
