Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy.

Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.

Role of Essential Oil-Based Mouthwashes in Controlling Gingivitis in Patients Undergoing Fixed Orthodontic Treatment. A Review of Clinical Trials.

Essential oil (EO)-based mouthwashes have been used for oral health maintenance due to their antimicrobial and anti-inflammatory properties. The aim was to review clinical trials that assessed the role of EO-based mouthwashes in controlling gingivitis in patients undergoing fixed orthodontic treatment (OT). The Patients, Interventions, Control and Outcome (PICO) format was based on the following: (a) P: Patients undergoing fixed OT (b) Intervention: EO-based mouth-wash; Control: Mouthwashes that did not contain EOs or no mouthwash (d) Outcome: Control of gingivitis measured by clinical indices. Databases were searched manually and electronically up to and including May 2021 using different medical subject subheadings. Data screening and extraction were performed. The risk of bias within randomized controlled trials was assessed using the revised Cochrane Collaboration's risk of bias tool (RoB 2). The Risk of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool was used for non-randomized controlled trials. Disagreements related to literature search and RoB evaluations were resolved via discussion. Six clinical studies were included. Four studies showed that Listerine® is effective in controlling gingivitis in patients undergoing fixed OT. One study reported that the use of 5% Fructus mume mouthwash resulted in a significant reduction in gingival bleeding. Two mouthwashes that contained 1% Matricaria chamomilla L. and 0.5% Zingiber officinale were also found to be efficient in controlling gingival bleeding. Four, one and one studies had a low, moderate and high RoB, respectively. In conclusion, EO-based mouthwashes seem to be effective for the management of gingivitis among patients undergoing fixed OT. Further well-designed and power-adjusted clinical trials are needed.

Identification of novel alternative splice variants of the human L-DOPA decarboxylase (DDC) gene in human cancer cells, using high-throughput sequencing approaches.

The human L-DOPA decarboxylase (DDC) is a gene that has been in the center of research attention in many laboratories the last decades, due to its major implication in various disorders, including many types of cancer. In the current work, we used in-house developed RACE and high-throughput sequencing approaches, in order to detect and identify novel DDC transcripts. Bioinformatic analysis revealed new alternative splicing events that support the existence of novel DDC transcripts. As a result, a total of 14 DDC splice variants were identified and their expression profile was investigated in a wide panel of human cancer cell lines. From all 14 novel DDC transcripts that were identified, 9 transcripts are predicted to encode new protein isoforms, while the remaining 5 are nonsense-mediated mRNA decay (NMD) candidates. Our results demonstrate that the human DDC gene undergoes complex processing leading to the figuration of multiple mRNA isoforms in cancer cells.