Prevention of tick-borne diseases: challenge to recent medicine.

Abstract: Ticks represent important vectors and reservoirs of pathogens, causing a number of diseases in humans and animals, and significant damage to livestock every year. Modern research into protection against ticks and tick-borne diseases focuses mainly on the feeding stage, i.e. the period when ticks take their blood meal from their hosts during which pathogens are transmitted. Physiological functions in ticks, such as food intake, saliva production, reproduction, development, and others are under control of neuropeptides and peptide hormones which may be involved in pathogen transmission that cause Lyme borreliosis or tick-borne encephalitis. According to current knowledge, ticks are not reservoirs or vectors for the spread of COVID-19 disease. The search for new vaccination methods to protect against ticks and their transmissible pathogens is a challenge for current science in view of global changes, including the increasing migration of the human population. Highlights: • Tick-borne diseases have an increasing incidence due to climate change and increased human migration• To date, there is no evidence of transmission of coronavirus COVID-19 by tick as a vector• To date, there are only a few modern, effective, and actively- used vaccines against ticks or tick-borne diseases• Neuropeptides and their receptors expressed in ticks may be potentially used for vaccine design.

Platelet Mitochondrial Bioenergetics Reprogramming in Patients with Urothelial Carcinoma.

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q10 (CoQ10) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and ß-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ10 level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ10 cycle (Q-junction) to CI.

Plasma thiobarbituric acid reactive substances predicts survival in chemotherapy naïve patients with metastatic urothelial carcinoma.

Oxidative stress plays a significant role in development and progression of cancer, including urothelial carcinomas. TBARS (Thiobarbituric acid reactive substances) represents a marker of oxidative stress increased in various diseases. In this prospective study, we tested the hypothesis of plasma TBARS concentration and correlation with survival in chemotherapy naïve MUC (metastatic urothelial carcinoma) patients. Most of subjects (N = 65) were treated with gemcitabine and cisplatin (GC) chemotherapy. Performance status ECOG ≥2 had 11 patients, visceral metastases were present in 43. Based upon the mean of plasma TBARS, subjects were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared by log-rank test. At median follow-up of 9.6 months, 65 patients experienced progression and 64 died. Subjects with low TBARS had significantly better PFS (HR 0.51) and OS (HR 0.44) opposed to high TBARS. Patients with low TBARS had significantly higher rate of neutropenia G4 and less liver involvement. High TBARS correlated with BMI above 30 kg/m2. Performance status and plasma TBARS were proven to be independent predictors of PFS and OS. In this study, high TBARS in MUC patients were associated with poor survival, likely due to more aggressive disease activity as reflected in increased liver involvement. Therefore, this biomarker could be used in clinical practice for early identification of patients with worse prognosis, better patient stratification, and treatment decision making.