Post-traumatic stress disorder: Impact on heart rate variability and glucose metabolism

Background and Aims: Due to the war in Ukraine, the incidence of post-traumatic stress disorder (PTSD) is increasing. PTSD is a significant social problem, as it is a serious risk factor for depression, suicide, and functional dysregulation of internal organs. This study aimed to analyze the results of a questionnaire and the clinical and paraclinical manifestations of PTSD.
Methods: A total of 172 people were evaluated, and 40 patients with PTSD were included in the study. Patients were aged 40-50 years with a BMI of 28.1±0.4 kg/m2. Glycated hemoglobin A1c, glucose, immunoreactive insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels were measured. A digital ECG device with software to analyze heart rate variability (HRV), was used to record short-term ECG (5 minutes in the supine position and 6 minutes in the orthostatic test). These were used to figure out the time-domain and frequency-domain parameters of HRV.
Results: According to the obtained data, a high level of anxiety was recorded in 11 respondents (27.5%), an average level in 8 patients (20.0%), a moderate level in 9 people (22.5%), and a minimal level among 12 respondents (30.0%). The pattern of HRV changes shows that the parasympathetic branch of the autonomic nervous system (ANS) is suppressed (-11.9%, p<0.05), there is low overall spectral power, and the ratio of low-frequency to high-frequency bands goes up (+7.6%, p<0.05). This means that the sympathetic branch of the ANS is more dominant in people with PTSD. Patients with PTSD were characterized by higher HOMA-IR indices (5.1±0.7 vs. 2.4±0.6, p<0.001). Eight people with PTSD manifested newly diagnosed type 2 diabetes mellitus (T2DM).
Conclusions: PTSD is characterized by a disturbed HRV, an increased sympathetic response of the ANS, IR parameters, and an increased incidence of T2DM development. The obtained results provide insights into the mechanisms underlying the systemic consequences of PTSD.
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New 4-thiazolidinone-based molecules Les-2769 and Les-3266 as possible PPARγ modulators

Development of cancer drug-resistance is still an ongoing problem in the modern anticancer treatment. Therefore, there is a need to search for a new active substance, which may become a potential anticancer agent. 4-Thiazolidinones are well-described substances with cytotoxicity against cancer cells in vitro. Therefore, the aim of this study was to evaluate the effect of two 4-thiazolidinone-based derivatives (Les-2769 and Les-3266) on the PPARγ-dependent cytotoxicity in normal human skin fibroblasts (BJ) and squamous cell carcinoma (SCC-15) in vitro. The data obtained showed a cytotoxic effect of Les-2769 and Les-3266 used in micromolar concentrations on SCC-15 and BJ cells, manifesting by a decrease in the metabolic activity, an increase in the release of lactate dehydrogenase, and caspase-3 activity. The co-treatment of the cells with Les-3266 and an antagonist (GW9662) or an agonist (rosiglitazone) of the PPARγ receptor induced changes in the above-mentioned parameters in the BJ and SCC-15 cells, compared to the Les-3266 alone exposure; this was not found in the Les-2769-treated cells. The further analysis of the compounds indicated changes in the expression of the PPARγ, KI67, and NF-κB genes. Moreover, the tested compounds caused an increase in the level of PPARγ mRNA expression in a similar way to rosiglitazone in SCC-15, which may indicate the affinity of the compounds for PPARγ. Molecular docking is consistent with experimental in vitro data about the potential agonistic activity of Les-2769 and Les-3266 towards PPARγ receptors. Summarizing, the anticancer effect of both compounds was observed in the SCC-15 cells in vitro; moreover, the mechanism of action of Les-3266 in cells is mediated probably by interaction with the PPARγ receptor pathway, which needs in-depth study. 

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