SUMMARY OBJECTIVE: This study aimed to investigate the expression levels of sirtuin 2 and sirtuin 7 in the placenta accreta spectrum to reveal their role in its pathogenesis. METHODS: A total of 30 placenta accreta spectrum, 20 placenta previa, and 30 controls were experienced. The sirtuin 2 and sirtuin 7 expression levels in the placentas of these groups were determined by Western blot. sirtuin 2 and sirtuin 7 serum levels in the maternal and fetal cord blood were examined by enzyme-linked immunosorbent assay. RESULTS: It was found that sirtuin 7 in placenta accreta spectrum was significantly lower in the placenta compared to the control and placenta previa groups (p<0.05). However, a significant difference was not observed between the sirtuin 2 and sirtuin 7 levels in the maternal and fetal cord serum samples of those three groups (p>0.05). CONCLUSION: Sirtuin 7 may play an important role in the formation of placenta accreta spectrum. The effect of decreased expression of sirtuin 7 might be tissue-dependent in the placenta accreta spectrum and needs to be investigated further.

ABSTRACT: Theileria parva is the causative agent of East Coast Fever (ECF), a tick borne disease, which results in major economic losses in cattle. Major problems in dealing with this illness are the high cost of drugs, development of resistance, and absence of effective vaccines. Thus, exploiting new targets for cost effective and higher therapeutic value drugs are imperative. Glycolysis is the main pathway for generation of ATP in T. parva, given its development inside erythrocytes. Thus, the enzymes of this pathway may prove potential targets for designing new-generation anti-theilerials. Lactate dehydrogenase of T. parva (TpLDH) has the highest activity of all glycolytic enzymes and thus we selected this enzyme as the potential therapeutic target. Our study is the first to report the isolation, removal of introns through directed mutagenesis, and cloning of TpLDH and showing that amino acid insertions or deletions most notably corresponded to a 5-amino acid sequence (Asn-91A, Glu-91B, Glu-91C, Trp-91D, Asn-91E) between Ser-91 ve Arg-92 of the enzyme. This region is also present in other apicomplexan such as Babesia bovis, a pathogen of cattle and Plasmodium falciparum, a human pathogen. Providing as the attachment site for the enzyme inhibitors and not being present in LDH of respective hosts, we propose this site as an attractive drug target. The work here is expected to lead new studies on detailed structural and kinetic aspects of apicomplexan LDHs and development of new inhibitors.

ABSTRACT The apicomplexan parasite Theileria parva, the causative agent of ECF, is an important pathogen affecting both domestic and wild animals, causing major economic losses in the world. Problems such as high cost of drugs, development of resistance, and absence of effective vaccines prevent effective combating of the pathogen. Thus, it is necessary to explore new targets for affordable and higher therapeutic value drugs. 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is vital to the organism and therefore has been selected as a target for developing antitheilerial drugs. In this study, the 3D structure of TpDXR was identified by template-based in silico homology modelling method, the constructed model was validated and structurally analysed, and possible ligand binding pockets were identified for the first time in the literature. A reliable 3D model for TpLDH was modelled by using 3AU9 chain ‘A’ Plasmodium falciparum as a template. The obtained result showed that the model has a good resolution structure with 86.768 overall quality factor and a -9.15 z-score for TpDXR. The present study promises the possibility of exploiting new and safe inhibitors using the structure-based drug design that is effective against ECF through docking studies.