Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

In this study, we characterized a collection of clinical samples obtained from Syrian and Turkish patients with cutaneous leishmaniasis using internal transcribed spacer 1 (ITS1) sequences. All obtained sequences belonged to Leishmania tropica. Combining them with those available from GenBank allowed us performing a broad-scale analysis of genetic diversity for this species. We demonstrated that L. tropica has a complex phylogeographic pattern with some haplotypes being widespread across endemic countries and others restricted to particular regions. We hypothesize that at least some of them may be associated with alternative vectors or animal reservoirs.

Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host′s phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite′s survival in the host. One of the interesting possibilities is that LmDUSP1 may target host′s substrate(s), thereby affecting its signal transduction pathways.

The Leishmania donovani species complex consists of all L. donovani and L. infantum strains mainly responsible for visceral leishmaniasis (VL). It was suggested that genome rearrangements in Leishmania spp. occur very often, thus enabling parasites to adapt to the different environmental conditions. Some of these rearrangements may be directly linked to the virulence or explain the reduced efficacy of antimonial drugs in some isolates. In the current study, we focused on a large-scale analysis of putative gene conversion events using publicly available datasets. Previous population study of L. donovani suggested that population variability of L. donovani is relatively low, however the authors used masking procedures and strict read selection criteria. We decided to re-analyze DNA-seq data without masking sequences, because we were interested in the most dynamic fraction of the genome. The majority of samples have an excess of putative gene conversion/recombination events in the noncoding regions, however we found an overall excess of putative intrachromosomal gene conversion/recombination in the protein coding genes, compared to putative interchromosomal gene conversion/recombination events.

This in vitro study was performed to investigate the changes in nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels in human monocytic (U937) cells infected with Encephalitozoon intestinalis. E. intestinalis was first cultured in the African green monkey renal epithelial (Vero) cells to obtain sufficient amount of parasite for the study. U937 human macrophage cell line and E. intestinalis 50506 (ATCC) strain were used in the study. U937 macrophages were infected with 5x106 spores after stimulation with Phorbol 12-Myristate 13-Acetate (PMA) and uninfected U937 cells were used as control. Culture media were collected at the 6th, 12th, and 24th hour after infection to determine NO, MDA, TAC, TNF-α and IL-10 levels. NO levels significantly increased at the 6th, 12th and 24th hour. There was no significant difference in MDA and TAC levels at the 6th and 12th hour, but a significant increase in MDA, and a significant decrease in TAC was observed at the 24th hour. TNF-α levels did not differ in all sampling times, and IL-10 level decreased only at the 6th hour. In conclusion, E. intestinalis caused oxidative stress by increasing the levels of oxidants (NO and MDA) and by suppressing TAC level without no significant changes in cytokine levels in U937 cell line.

Encephalitozoon intestinalis (E. intestinalis) is a parasite that causes opportunistic infections that can cause death in immune compromised patients. The aim of this study was to determine the effect of parasite on genes involved in host cell apoptosis. The CaCo cells were infected with E. intestinalis 50506 (ATCC) strain. Apoptosis was induced in both control and parasite-infected groups after infection. RNA isolation and cDNA extraction were then performed. Changes in the expression of genes involved in apoptotic pathways were evaluated quantitatively (qPCR) by Real-Time PCR. The obtained data were analyzed by 2^-ΔΔCt method. E. intestinalis inhibits the CASP6, DR4, DR5, DCR2 genes that regulate the transcription of the genes known as the death gene of cells in CaCo cells. TP53 regulates the transcription of certain genes involved in cell death. DR4, DR5 and DCR2 are inhibited by the introduction of E. intestinalis into the cell. Caspase 6 is one of the caspases that induces apoptosis. As can be seen from the activation of these genes, E. intestinalis inhibits transcription genes in the pro-apoptotic pathway of the cell. We think that this parasite, which is commonly found in cancer patients, should be investigated for the effect of drug resistance in cancer treatment. This study was supported by Erciyes University. Project ID: TCD-2016-7042.