The effect of two COVID-19 lockdowns on physical activity of school-age children.

The introduction of strict quarantine restrictions in many countries initiated a direction in science to study the behavioral characteristics of children and adolescents during the social isolation at the population level. We present our observations during the two lockdowns in Ukraine. The objective of this study was to determine: a) the level of light (LPA) and moderate-to-vigorous (MVPA) physical activity among school-age children, and b) the impact of the external and internal factors on their physical activity during the lockdown. Global Physical Activity Questionnaire (GPAQ) as part of our questionnaire Q-RAPH was used. Parents of 1091 children 6-18 years old (54% boys) filled Q-RAPH at two measurement points in 2020 and 2021. After performing ANCOVA and logistic regression, we found a significant decrease in MVPA by 12.7% in 2021 compared to 2020 (p â€‹< â€‹0.001) while LPA was about 1.5 â€‹h a day during both periods. The proportion of children who reach the recommended levels of MVPA also decreased by 13.7% in 2021 (p â€‹< â€‹0.001). Factors negatively affecting the achievement of 60 â€‹min a day of MVPA were female gender, chronic diseases, overweight/obesity, non-participation in organized sports, and a decrease in the average air temperature. This study evidences the insufficient level of preventive measures and requires an intensification of health education among the Ukrainian population. When developing preventive measures, special attention should be paid to groups vulnerable to MVPA reduction as children who have chronic diseases and/or overweight/obesity as well as non-participation in sports.

Suppression of systemic inflammation and signs of acute and chronic cholangitis by multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione.

An aberrant activity of growth factor receptors followed by excessive cell proliferation plays a significant role in pathogenesis of cholangitis. Therefore, inhibition of these processes could be a fruitful therapeutic strategy. The effects of multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione (MI-1) on the hepatic and systemic manifestations of acute and chronic cholangitis in rats were addressed. MI-1 (2.7 mg/kg per day) was applied to male rats that experienced α-naphthylisothiocyanate-induced acute (3 days) or chronic (28 days) cholangitis. Liver autopsy samples, blood serum markers, and leukograms were studied. MI-1 localization in liver cells and its impact on viability of HepG2 (human hepatoma), HL60 (human leukemia), and NIH3T3 (normal murine fibroblasts) cell lines and lymphocytes of human peripheral blood (MTT, DNA fragmentation, DNA comet assays, Propidium Iodide staining) were assessed. Under both acute and chronic cholangitis, MI-1 substantially reduced liver injury, fibrosis, and inflammatory scores (by 46-86%) and normalized blood serum markers and leukograms. Moreover, these effects were preserved after a 28-day recovery period (without any treatment). MI-1 inhibited the HL60, HepG2 cells, and human lymphocytes viability (IC50 0.6, 9.5 and 8.3 µg/ml, respectively), while NIH3T3 cells were resistant to that. Additionally, HepG2 cells and lymphocytes being incubated with MI-1 demonstrated insignificant pro-apoptotic and pro-necrotic changes and DNA single-strand breaks, suggesting that MI-1 effects in liver might be partly caused by its cytotoxic action towards liver cells and lymphocytes. In conclusion, MI-1 attenuated the systemic inflammation and signs of acute and chronic cholangitis partly through cytotoxicity towards cells of hepatic and leukocytic origin.

Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis.

BACKGROUND: A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics. AIMS: The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered. METHODS: Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS. RESULTS: On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner. CONCLUSION: Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.

Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety.

Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs' action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes. PDs entered into electrostatic interactions with polar groups of phospholipid heads in cell membrane, and the power of interaction depended on the nature of PD radical substituents (greater for MI-1 and smaller for D1). Partial intercalation of MI-1 into the membrane hydrophobic zone also occurred. PDs concentrations induced apoptosis in malignant cells but normal ones had different sensitivity to those. MI-1 and D1 acted like antioxidants in inflamed colonic tissue, as evidenced by reduce of lipid and protein peroxidation products (by 43-67%) and increase of superoxide dismutase activity (by 40 and 58%) with restoring these values to control ones. MI-1 restored reduced haemoglobin and normalised elevated platelets and monocytes in settings of colorectal cancer, whereas D1 normalised only platelets. Thus, MI-1 and D1 could be used as competitive inhibitors of EGFR and VEGFR and antioxidants, which might contribute to realisation of their anti-inflammatory, proapoptotic and antitumor activity.

Water-soluble pristine C60 fullerene attenuates acetaminophen-induced liver injury.

Introduction: Oxidative stress has been suggested as the main trigger and pathological mechanism of toxic liver injury. Effects of powerful free radical scavenger С60 fullerene on rat liver injury and liver cells (HepG2 line) were aimed to be discovered. Methods: Acute liver injury (ALI) was simulated by single acetaminophen (APAP, 1000 mg/kg) administration, on a chronic CLI, by 4 weekly APAP administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS; initial concentration 0.15 mg/mL) was administered per os or intraperitoneally at a dose of 0.5 mg/kg (ALI) or 0.25 mg/kg (CLI) daily for 2 or 28 days, respectively, after first APAP dose. Animals were sacrificed at 24th hour after the last dose. Biochemical markers of blood serum and liver autopsies were analyzed. EGFR expression in HepG2 cells after 48-hour incubation with C60FAS was assessed. Results: Increase of serum conjugated and unconjugated bilirubin (up to 1.4-3.7 times), ALT (by 31-37%), and AST (by 18%) in non-treated ALI and CLI rats were observed, suggesting the hepatitis (confirmed by histological analysis). Liver morphological state (ALI, CLI), ALT (ALI and CLI), bilirubin (CLI), α-amylase, and creatinine (ALI) were normalized with C60FAS administration in both ways, which may indicate its protective impact on liver. However, unconjugated bilirubin sharply increased in ALI animals receiving C60FAS (up to 12 times compared to control), suggesting the augmentation of bilirubin metabolism. Furthermore, C60FAS inhibited EGFR expression in HepG2 cells in a dose-dependent manner. Conclusion: C60FAS could partially correct acute and chronic toxic liver injury, however, it could not normalize bilirubin metabolism after acute exposure.