Illuminating (HTLV-1)-induced adult T-cell leukemia/lymphoma transcriptomic signature: A systems virology approach.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis malignancy of peripheral T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The low survival rates observed in the patients are the result of the lack of sufficient knowledge about the disease pathogenesis. METHODS: In the present study, we first identified differentially expressed genes in ATLL patients and the cellular signaling pathways affected by them. Then, genes of these pathways were subjected to more comprehensive evaluations, including WGCNA and module validation studies on five external datasets. Finally, potential biomarkers were selected for qRT-PCR validation. RESULTS: Thirteen signaling pathways, including Apoptosis, Human T-cell leukemia virus 1 infection, IL-17 signaling pathway, pathways in cancer, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, and seven others were selected for deeper investigations. Results of our in-depth bioinformatics evaluations, highlighted pathways related to regulation of immune responses, T-cell receptor and activation, regulation of cell signaling receptors and messengers, Wnt signaling pathway, and apoptosis as key players in ATLL pathogenesis. MAPK3, PIK3CD, KRAS, NFKB1, TNF, PLCB3, PLCB2, PLCB1, MAPK11, JUN, ITPR1, ADCY1, GNAQ, ADCY3, ADCY4, CHEK1, CCND1, SOS2, BAX, FOS and GNA12 were identified as possible biomarkers. Upregulation of ADCY1 and ADCY3 genes was confirmed via qRT-PCR. CONCLUSIONS: In this study, we performed a deep bioinformatic examination on a limited set of genes with high probabilities of involvement in the pathogenesis of ATLL. Our results highlighted signaling pathways and genes with potential key roles in disease formation and resistance against current treatment strategies. Further studies are required to test the possible benefits of highlighted genes as biomarkers and targets of treatment.

Bioactivities of rose-scented geranium nanoemulsions against the larvae of Anopheles stephensi and their gut bacteria.

Anopheles stephensi with three different biotypes is a major vector of malaria in Asia. It breeds in a wide range of habitats. Therefore, safer and more sustainable methods are needed to control its immature stages rather than chemical pesticides. The larvicidal and antibacterial properties of the Pelargonium roseum essential oil (PREO) formulations were investigated against mysorensis and intermediate forms of An. stephensi in laboratory conditions. A series of nanoemulsions containing different amounts of PREO, equivalent to the calculated LC50 values for each An. stephensi form, and various quantities of surfactants and co-surfactants were developed. The physical and morphological properties of the most lethal formulations were also determined. PREO and its major components, i.e. citronellol (21.34%), L-menthone (6.41%), linalool (4.214%), and geraniol (2.19%), showed potent larvicidal activity against the studied mosquitoes. The LC50/90 values for mysorensis and intermediate forms were computed as 11.44/42.42 ppm and 12.55/47.69 ppm, respectively. The F48/F44 nanoformulations with 94% and 88% lethality for the mysorensis and intermediate forms were designated as optimized formulations. The droplet size, polydispersity index, and zeta-potential for F48/F44 were determined as 172.8/90.95 nm, 0.123/0.183, and -1.08/-2.08 mV, respectively. These results were also confirmed by TEM analysis. Prepared formulations displayed antibacterial activity against larval gut bacteria in the following order of decreasing inhibitory: LC90, optimized nanoemulsions, and LC50. PREO-based formulations were more effective against mysorensis than intermediate. Compared to the crude PREO, the overall larvicidal activity of all nanoformulations boosted by 20% and the optimized formulations by 50%. The sensitivity of insect gut bacteria may be a crucial factor in determining the outcome of the effect of toxins on target insects. The formulations designed in the present study may be a good option as a potent and selective larvicide for An. stephensi.