Search

In the spring 2022, the number of cases of severe acute hepatitis of unknown etiology was unusual increased in Europe. As an immediate response, the World health organization recommended active efforts to identify such cases at the international level. For monitoring of acute hepatitis in Moscow, patients with suspected liver disease were sent to Infectious Diseases Clinical Hospital No. 1. The goal: study of the structure of diseases occurring with liver damage in children hospitalized in 2022. Materials and methods: analysis of medical records of children hospitalized with a diagnosis of hepatitis from May 1 to December 31, 2022. Еpidemiological data (age, gender, parenteral manipulations, contacts with patients, travel abroad), clinical (fever, jaundice, etc.), laboratory parameters were assessed. Results: A total of 164 completed cases of hepatitis in children aged 5 months to 17 years were analyzed. 36 children met the criteria for probable severe acute hepatitis of unknown etiology. Age median was 7 years [2.25;11]. Girls made up more than half (21 (58.3%). Non-infectious genesis was established in 15 (41.6%). The infectious disease was verified in 11 (30.5%), of which adenoviral infection was detected in 2 children. In 9 (25%) children the etiology of hepatitis was not established. Conclusion. Various infectious and non-infectious diseases among hospitalized children lead to a significant increase in liver transaminases. Most acute hepatitis with unspecified etiology proceeded as an acute infectious disease and ended in recovery. The role of adenoviruses in the development of severe hepatitis in children was not confirmed in our study.

Objective. Mitochondrial injury plays a central role in neuronal death following ischemic stroke. In the present study, we investigated effects of ethylmethylhydroxypyridine succinate on a microstroke-induced mitochondria swelling, a hallmark of mitochondrial injury.Materials and Methods. Ischemic microstroke was induced in Thy1-CFP-MitoS mice expressing cyano fluorescent protein (CFP) in brain mitochondria by impulse infrared laser. Ethylmethylhydroxypyridine succinate 25 mg/kg or saline (control) were administered i.p. at 30 min after the stroke onset. A period of observation was 48 h. Brain images were obtained by two photon laser fluorescent microscopy and analyzed using a software developed in Neurotar Ltd (Finland). Nonparametric Mann-Whitney-Wilcoxon test was used for te statistical analysis of results.Results. Microstroke resulted in mitochondria swelling, i.e. injury, in the zone surrounding the thrombus. The most profound changes of mitochondrial morphology were observed at 2 h from the stroke onset. Ethylmethylhydroxypyridine succinate significantly reduces the stroke-induced swelling at 1 h (p

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of children, characterized by selective death of neocortical neurons. To understand early disease mechanisms in INCL, we have studied Ppt1Deltaex4 knock-out mouse neurons in culture and acute brain slices. Global transcript profiling showed deregulation of key neuronal functions in knock-out mice including cholesterol metabolism, neuronal maturation, and calcium homeostasis. Cholesterol metabolism showed major changes; sterol biosynthesis was enhanced and steady-state amounts of sterols were altered at the cellular level. Changes were also present in early maturation of Ppt1Deltaex4 neurons indicated by increased proliferative capacity of neuronal stem cells. Knock-out neurons presented unaltered electrophysiological properties suggesting uncompromised synaptic function in young animals. However, knock-out neurons exhibited more efficient recovery from glutamate-induced calcium transients, possibly indicating neuroprotective activation. This study established that the neuronal deregulation in INCL is linked to neuronal maturation, lipid metabolism and calcium homeostasis.

Abstract: Neuronal ceroid lipofuscinoses (NCLs) are a group of genetic childhood-onset progressive brain diseases characterized by a decline in mental and motor capacities, epilepsy, visual loss and premature death. Using patch clamp, fluorescence imaging and caged Ca2+ photolysis, we evaluated the mechanisms of neuronal Ca2+ clearance in Cln8 mnd mice, a model of the human NCL caused by mutations in the CLN8 gene. In Cln8 mnd hippocampal slices, Ca2+ clearance efficiency in interneurons and, to some extent, principal neurons declined with age. In cultured Cln8 mnd hippocampal neurons, clearance of large Ca2+ loads was inefficient due to impaired mitochondrial Ca2+ uptake. In contrast, neither Ca2+ uptake by sarco/endoplasmic reticulum Ca2+ ATPase, nor Ca2+ extrusion through plasma membrane was affected by the Cln8 mutation. Excitotoxic glutamate challenge caused Ca2+ deregulation more readily in Cln8 mnd than in wt neurons. We propose that neurodegeneration in human CLN8 disorders is primarily caused by reduced mitochondrial Ca2+ buffering capacity. [Copyright &y& Elsevier]

Background/aim: Colorectal cancer is currently the third leading cause of cancer-related deaths and recently, alternative splicing has risen as its important regulator and potential treatment target. In the present study, we analyzed gene expression of the MBNL family of regulators of alternative splicing in various stages of colorectal cancer development, together with the MBNL-target splicing events in FOXP1 and EPB41L3 genes and tumor-related CD44 variants., Materials and Methods: Samples of tumor tissue and non-malignant mucosa from 108 patients were collected. After RNA isolation and reverse transcription, the relative gene expression of a selected gene panel was tested by quantitative real-time PCR, followed by statistical analysis., Results: MBNL expression was decreased in tumor tissue compared to non-tumor mucosa. In addition, lower expression was observed for the variants of FOXP1 and EPB41L3, while higher expression in tumor tissue was detected both for total CD44 and its cancer-related variants 3 and 6. Transcript levels of the MBNL genes were not found to be related to any of the studied clinicopathological characteristics. Multiple significant associations were identified in the target gene panel, including higher transcript levels of FOXP1 and CD44v3 in patients with distant metastases and connections between recurrence-free survival and altered levels of FOXP1 and CD44v3., Conclusion: Our results identified for the first-time deregulation of MBNL genes in colorectal cancer. Down-regulation of their transcripts in tumor tissue compared to matched non-tumor mucosa can lead to transition of alternative splicing patterns towards a less differentiated phenotype, which highlights the importance of alternative splicing regulation for tumor growth and propagation., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)