Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.
26 March 2023 in Journal of Forensic and Legal Medicine
Isolated splenic peliosis is an extremely rare condition characterized by the presence of multiple blood-filled cavities, occasionally resulting in non-traumatic splenic rupture with fatal bleeding. In our case, a 64-year-old man was brought by ambulance due to weakness and abdominal pain without nausea or febrility. On clinical examination, the patient was sensitive to palpation with significant tenderness over the abdomen but no associated features of peritonitis. He collapsed during the imaging examination and became unconscious and asystolic. Cardiopulmonary resuscitation was not successful. The patient died approximately within 2 hours of admission to the hospital. Postmortal examination showed 2800 ml of intraperitoneal blood with clots and a laceration of the lower pole of the spleen. Macroscopic examination of the spleen revealed huge nodular splenomegaly, measuring 21 cm x 19 cm x 5 cm, weighing 755 g. On the cut surfaces, multiple randomly distributed blood-filled cavities ranging from 0,5 to 2 cm in diameter were seen. At microscopic examination, the specimens showed multiple irregular haemorrhagic cyst-like lesions that were not lined by any epithelium or sinusoidal endothelium, consistent with the diagnosis of peliosis lienis. Although the condition is often clinically silent, the forensic pathological significance arises from the differential diagnosis of resultant intraperitoneal haemorrhage and sudden death, mimicking a violent death.
Background: Ischemic-reperfusion damage of cardiomyocytes due to myocardial infarction (MI) often leads to the death of an individual. Premenopausal women have been observed to have a significantly lower risk of cardiovascular disease (CVD) than men of the same age. In menopausal women, this trend is significantly reversed, and the risk of CVD increases up to 10-fold. Estrogens affect the development and function of the heart muscle, and as they decrease, the risk and poor prognosis of CVD increase. This study is focused on the effects of estrogen supplementation on morbidity, vitality, and NCX1 expression after MI on a model system. Methods: In this study, female Sprague Dawley rats (n = 58), which were divided into three experimental groups (NN—control group, non-supplemented; OVX-N—ovariectomized, non-supplemented; OVX-S—ovariectomized, supplemented), received left thoracotomy in the fourth intercostal space. The left anterior descendent coronary artery was ligated 2 mm from its origin with an 8.0 suture. An immunohistological analysis as well as an RT-PCR analysis of NCX1 expression were performed. Results: A higher survival rate was recorded in the OVX-N group (86%) in comparison with the OVX-S group (53%) (p < 0.05). In addition, higher NCX1 expression 7 days/14 days after MI in the OVX-S group in comparison with the NN and OVX-N (p < 0.001 and p < 0.05) groups was recorded. Seven days after MI, a significantly higher expression (p < 0.005) of mRNA NCX1 in the OVX-N group was also recorded in comparison with the NN group. Conclusions: This study provides a comprehensive description of the effect of estrogen supplementation on NCX1 expression and overall vitality in ovariectomized rats that survived MI.
Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 106 dm3mol−1 to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood–brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.
Central nervous system (CNS) tumors represent a heterogeneous group of neoplasms associated with significant morbidity and mortality despite their relatively low incidence. Advances in the fifth edition of the World Health Organization (WHO) classification have emphasized the integration of histopathological, immunohistochemical, and molecular features, fundamentally transforming diagnostic and prognostic frameworks in neuro-oncology. This manuscript aims to provide an overview of CNS tumor biology, focusing on key diagnostic markers, genetic and epigenetic alterations, and emerging therapeutic strategies. It further describes recent advances in multi-omics approaches and artificial intelligence, which enable deeper characterization of tumor heterogeneity and support the development of precision medicine strategies. Finally, current and emerging therapeutic modalities, including combination therapies, targeted treatments, and novel molecular targets, are examined with emphasis on overcoming resistance mechanisms and improving clinical outcomes. Overall, the integration of molecular biology, advanced diagnostics, and innovative therapeutic approaches represents a critical step toward personalized management of CNS tumors and improved patient survival.