Assessment of the Acute Toxicity of Chlorophyllin and Trolox for the Possibility of Studying Their Radioprotective Properties.

The acute toxicity of chlorophyllin and trolox upon intraperitoneal injection of their solutions was studied in male ICR (CD-1) mice. The LD50 of chlorophyllin was found to be 633±37.2 µg/g body weight, which is lower than the LD50 of established radioprotectors. Trolox is technically non-toxic under the conditions of our study. The results obtained highlight the need for a detailed study of the radioprotective properties of trolox and chlorophyllin.

[Optical coherence tomography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya v diagnostike rasseyannogo skleroza.

Multiple sclerosis (MS) is a chronic autoimmune-inflammatory and neurodegenerative disease. PURPOSE: This study explores the main structural changes in patients with MS and their relationships with the activity and type of disease course. MATERIAL AND METHODS: This prospective study included 159 patients (318 eyes) with an established diagnosis of MS: group (44 eyes; 13.84%) - relapsing-remitting type MS (RRMS) lasting up to 1 year without a history of optic neuritis (ON); group 2 (30 eyes; 9.43%) - RRMS up to 1 year with ON; group 3 (56 eyes; 17.61%) - RRMS lasting from 1 to 10 years without ON; group 4 (38 eyes; 11.95%) - RRMS from 1 to 10 years with ON; group 5 (49 eyes; 15.41%) - RRMS >10 years without ON; group 6 (37 eyes; 11.63%) - RRMS >10 years with ON; group 7 (34 eyes; 10.69%) - secondary progressive multiple sclerosis (SPMS) without ON; group 8 (30 eyes; 9.43%) - SPMS with ON. Patients underwent standard ophthalmological examinations, including optical coherence tomography. RESULTS: A decrease in structural parameters was diagnosed, progressing with the duration of the disease and the presence of ON: the minimum values of mGCL+IPL (65.83±9.14 µm) and mSNFL (76.37±14.77 µm) were detected in the group with SPMS with ON. High inverse correlations of EDSS with mGCL+IPL and mRNFL were demonstrated, with maximum in the group with the longest duration of MS without ON (-0.48 and -0.52 (p=0.01), respectively). CONCLUSION: Changes in the thickness of the structural parameters of the retina, measured by OCT, can be considered as a predictor of the course of MS.

Protocol for Seahorse analysis of ex vivo mouse brown and white adipose tissues.

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.

[Morphological features of an optic nerve in premature infants according to the optical coherence tomography data]. / Morfologicheskie osobennosti zritel'nogo nerva u nedonoshennykh detei po dannym opticheskoi kogerentnoi tomografii.

OBJECTIVE: To assess the morphological state of the visual analyzer in premature infants in long-term. MATERIAL AND METHODS: We examined 40 premature children (74 eyes) aged 10.3±2.92 years (gestational age (GA) 25-34 weeks, birth weight (BW) 690-2700 g). Twenty mature children (40 eyes), aged 10.8±3.05 years, were examined as a control group. The children underwent standard ophthalmologic examination, optical coherence tomography (OCT) and recording of visual evoked potentials (VEP). RESULTS: The thickness of retinal nerve fiber layer (RNFL) is less in preterm infants than in term infants, regardless of retinopathy of prematurity (ROP) and refraction (p<0.05). Thickness loss has an inverse proportion with the degree of hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH) (p<0.05). Retinal thickness in fovea is significantly greater in preterm infants and has a direct proportionality with the degree of IVH and the number of days on artificial lung ventilation (p<0.05). Moderate organic changes were detected in conduction pathways in 43.08% of premature infants according to VEP data. CONCLUSION: The use of OCT and recording of VEP may improve the quality of comprehensive neuro-ophthalmologic diagnosis in preterm infants. The thickness loss of RNFL can be expected in premature infants with HIE and IVH.

[Diagnostic criteria of death cause from low temperature in air and water established by traditional expert examination methods]. / Diagnosticheskie kriterii prichiny smerti ot deistviya nizkoi temperatury na vozdukhe i v vode, ustanavlivaemye s pomoshch'yu traditsionnykh metodov ekspertnogo issledovaniya.

Death from general hypothermia is one of the leading causes in the structure of violent death in the Russian Federation. OBJECTIVE: To clarify and supplement the complex of differential diagnostic macro- and microscopic signs of a fatal acute general cold trauma received when person is in the air and water. MATERIAL AND METHODS: The conclusions of forensic medical experts on the bodies of people who died from hypothermia in the air and in water (by 150 observations) were analyzed. Methods of descriptive statistics, calculation of the frequency ratio of signs' occurrence were used. RESULTS: The article provides quantitative assessment of occurrence (detection) rate of diagnostically significant signs established with the help of traditional methods of expert examination. A new classification of diagnostic death signs from hypothermia taking into account their differential diagnostic significance and reflecting the conditions of a person's stay in the air and water in the pre-mortem and post-mortem periods, as well as terminal period mechanisms is proposed. CONCLUSION: The established complexes of signs provide an objective basis for determining death cause in non-obvious conditions when cold exposure is expected to be one of the most damaging factors.

[Causal links in forensic medicine in cases of acute enteric infections]. / Prichinno-sledstvennye svyazi v sudebnoi meditsine v sluchayakh ostrykh kishechnykh infektsii.

One of the main tasks in expertise of living persons is to determine the harm caused to human health. According to the regulations, only harm to human health caused by an injury and causally related with it is taken into account in the forensic examination of a living person. The establishment of a causal link allows to assess correctly the harm severity caused to human health. In this respect, the study of the effect of biological damaging factor on human body (cause) and the result of this interaction (effect) is a new step in modern science. The article presents the analysis of data from the reports of the Russian Reference Center on monitoring of enteric infection agents for 2016-2021; the results of examinations of subjects who suffered from acute enteric infections for 2018-2019 to study causal links in forensic medicine in cases of acute intestinal infections.

Measurement of the Pion Form Factor with CMD-3 Detector and Its Implication to the Hadronic Contribution to Muon (g-2).

The cross section of the process e^{+}e^{-}→π^{+}π^{-} has been measured in the center-of-mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on an integrated luminosity of about 88 pb^{-1}, of which 62 pb^{-1} represent a complete dataset collected by CMD-3 at center-of-mass energies below 1 GeV. In the dominant region near the ρ resonance a systematic uncertainty of 0.7% was achieved. The implications of the presented results for the evaluation of the hadronic contribution to the anomalous magnetic moment of the muon are discussed.

[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

Machine learning identifies activation of RUNX/AP-1 as drivers of mesenchymal and fibrotic regulatory programs in gastric cancer.

Gastric cancer (GC) is the fifth most common cancer worldwide and is a heterogeneous disease. Among GC subtypes, the mesenchymal phenotype (Mes-like) is more invasive than the epithelial phenotype (Epi-like). Although gene expression of the epithelial-to-mesenchymal transition (EMT) has been studied, the regulatory landscape shaping this process is not fully understood. Here we use ATAC-seq and RNA-seq data from a compendium of GC cell lines and primary tumors to detect drivers of regulatory state changes and their transcriptional responses. Using the ATAC-seq data, we developed a machine learning approach to determine the transcription factors (TFs) regulating the subtypes of GC. We identified TFs driving the mesenchymal (RUNX2, ZEB1, SNAI2, AP-1 dimer) and the epithelial (GATA4, GATA6, KLF5, HNF4A, FOXA2, GRHL2) states in GC. We identified DNA copy number alterations associated with dysregulation of these TFs, specifically deletion of GATA4 and amplification of MAPK9 Comparisons with bulk and single-cell RNA-seq data sets identified activation toward fibroblast-like epigenomic and expression signatures in Mes-like GC. The activation of this mesenchymal fibrotic program is associated with differentially accessible DNA cis-regulatory elements flanking upregulated mesenchymal genes. These findings establish a map of TF activity in GC and highlight the role of copy number driven alterations in shaping epigenomic regulatory programs as potential drivers of GC heterogeneity and progression.

Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism.

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum.

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC), characterized by the absence of an interhemispheric white matter tract that connects distant cortical regions. Here, we find that neurons expressing SATB2, a determinant of callosal projection neuron (CPN) identity, show impaired maturation in ARID1B+/- neural organoids. Molecularly, a reduction in chromatin accessibility of genomic regions targeted by TCF-like, NFI-like, and ARID-like transcription factors drives the differential expression of genes required for corpus callosum (CC) development. Through an in vitro model of the CC tract, we demonstrate that this transcriptional dysregulation impairs the formation of long-range axonal projections, causing structural underconnectivity. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous axonogenesis defects in SATB2+ neurons as a cause of ACC in ARID1B patients.

Changes in the Transcription of Proliferation- and Apoptosis-Related Genes in Embryos in Women of Different Ages under the Influence of Extracellular Vesicles from Donor Follicular Fluid In Vitro.

We studied the influence of extracellular vesicles from the follicular fluid of a young donor on gene expression (MKI67, MYBL2, CCNB1, CCND1, CCNE1, CALM2, BAX, NDRG1, TP53I3, VEGF, VCAN, HAS2, CTSL2, PIBF1, RPL37, PFKP, GPX3, and AQP3) in embryos of women of different ages. According to nanoparticle tracking analysis data, the concentration of extracellular vesicles was 3.75±0.47×1011 particles/ml and the mean particle size was 138.78±9.90 nm. During co-culturing of the follicular fluid extracellular vesicles with blastocysts of young women, we observed significantly increased expression of mRNA for genes CTSL2, CCND1, CCNE1, VEGF and reduced expression of BAX gene mRNA in comparison with embryos in women of late reproductive age. We hypothesized that addition of extracellular vesicles of the oocyte follicular fluid from a young donor to the culture medium of embryos could slow down apoptosis process typical of blastocyst cells in women above 36 years.

Radioprotective Properties of Riboxin (Inosine) and Indralin under External Irradiation.

A comparative assessment of radioprotective properties of inosine nucleoside (riboxin) and recognized radioprotector indralin was carried out. We analyzed survival of male ICR CD-1 mice weighting 32.2±0.2 g exposed to external X-ray radiation at doses 6.5 and 6.75 Gy and receiving indralin at a dose of 100 or 150 µg/g body weight or riboxin (inosine) at a dose of 100 or 200 µg/g body weight before irradiation. The survival analysis was carried out by the Kaplan-Meier method. The significance was assessed by using the log-rank-test. Inosine showed a significant difference from the irradiated control only at a dose of 100 µg/g body weight at a radiation dose of 6.75 Gy. The survival of animals treated with indralin was significantly higher in comparison with not only the irradiated control group, but also with the groups receiving inosine.

Experimental Approaches to Scar Modeling through Mechanical Skin Damage and Chemical Burn in Sprague Dawley Rats.

Creating of a scar model in laboratory animals is the most acceptable option for the preclinical search of scar treatment. However, due to high skin regeneration rate in laboratory rodents, creating an optimal animal model of scar formation is a challenge. Here we describe five methods for modeling a scar tissue in rats that we have tested. These methods allowed achieving different histopathological features and different stages of skin scar formation.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

Repeatability and Agreement of 4 Biometers Measuring Corneal Astigmatism in Eyes With Irregular Corneal Astigmatism Component.

PURPOSE: To investigate the repeatability and agreement of corneal astigmatism measurements in eyes with irregular corneal astigmatism component (ICAC) using four devices: IOLMaster 700 biometer, Lenstar 900 biometer, iTrace, and Pentacam. DESIGN: Prospective cross-sectional reliability analysis. METHODS: Sixty-four eyes (52 patients) with ICAC were examined three times using the four devices. The eye with ICAC in this study is defined as the cornea has a certain degree of irregular astigmatism (asymmetric and/or skewed bowtie pattern of corneal topography according to corneal topography classification), accompanied with total corneal higher-order aberrations in the 4 mm zone of 0.3 µm or greater. Corneal astigmatism was evaluated using three categories: anterior corneal astigmatism (ACA), posterior corneal astigmatism, and total corneal astigmatism (TCA). The repeatability was determined using the ∆Ast (arithmetic mean of vector differences among three repeated corneal astigmatism measurements). Bland-Altman plots and astigmatism vector analyses were employed to assess agreement. RESULTS: The IOLMaster 700 (∆Ast = 0.27 ± 0.20 D) showcased higher repeatability in ACA measurements compared to iTrace (∆Ast = 0.37 ± 0.38 D, P = .040) and Pentacam (∆Ast = 0.50 ± 0.22 D, P < .001), and paralleled the performance of Lenstar 900 (∆Ast = 0.31 ± 0.26 D, P = .338). The Pentacam (∆Ast = 0.09 ± 0.07 D, P < .001) demonstrated superior repeatability in posterior corneal astigmatism, whereas the IOLMaster 700 (∆Ast = 0.33 ± 0.23 D, P < .001) excelled in TCA. The IOLMaster 700 exhibited good agreement with either Lenstar 900 or iTrace, characterized by narrow 95% limits of agreement and clinically acceptable vector differences. Conversely, vector differences between Pentacam and the other three devices in ACA and TCA measurements were clinically significant, exceeding 0.50 D (all P < .05). CONCLUSIONS: In terms of repeatability of corneal astigmatism measurements in eyes with ICAC, the IOLMaster 700 and Lenstar 900 outperformed iTrace and Pentacam. While the IOLMaster 700 can be used interchangeably with either Lenstar 900 or iTrace, the Pentacam is not interchangeable with the other three devices.

[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

[Structure of pediatric ophthalmic pathology in Uzbekistan]. / Struktura detskoi oftal'mopatologii v Uzbekistane.

PURPOSE: This study analyzes the structure of eye diseases in children of different age groups based on the materials of the ophthalmology department of the Tashkent Pediatric Medical Institute (TPMI) clinic for 2018-2021. MATERIAL AND METHODS: A retrospective analysis of statistical coupons was conducted, which included the medical records of 5613 patients of the ophthalmology department of the TPMI clinic. RESULTS: In the age structure of ophthalmopathology in children who received inpatient treatment at the TPMI clinic in 2018-2021, children aged 5 to 14 years (49.5%) and 1 to 5 years (30.7%) were significantly predominant. The proportion of patients under 1 year old was 11.2% and from 14 to 18 years old - 7.5%. Congenital glaucoma (41%) and lens diseases (30.4%) are characteristic of infants (from 0 to 1 year old); in patients aged 1 to 5 years, lens pathology (37%), congenital glaucoma (25.2%), and injuries (24.7%) were more common; in children aged 5 to 14 years, the pathology of the oculomotor apparatus (32%) and injuries (27.7%) prevailed; in the age group from 14 to 18 years, lens diseases (28.4%) and injuries of the organ of vision (28.1%) were detected more often. CONCLUSIONS: The revealed age aspects of nosologies are due to the timing of clinical manifestations of the pathology, late seeking ophthalmic care of parents, presence of a concomitant pathology in the child, which prevents surgical treatment. The results of the study will help optimize planned and emergency ophthalmological care for children in the regions of the republic.

[To the 100th anniversary of the birth of MD, PhD, professor Lyusik Oganesovna Barsegyants]. / K 100-letiyu so dnya rozhdeniya doktora meditsinskikh nauk, professora Lyusik Oganesovny Barsegyants.

The article presents information about the life and activity of the outstanding scientist, professor L.O. Barsegyants.