Host response to cholestyramine can be mediated by the gut microbiota.

The gut microbiota has been implicated as a major factor contributing to metabolic diseases and the response to drugs used for the treatment of such diseases. In this study, we tested the effect of cholestyramine, a bile acid sequestrant that reduces blood cholesterol, on the murine gut microbiota and metabolism. We also explored the hypothesis that some effects of this drug on systemic metabolism can be attributed to alterations in the gut microbiota.

Transkingdom Network Analysis (TkNA): a systems framework for inferring causal factors underlying host-microbiota and other multi-omic interactions.

We present Transkingdom Network Analysis (TkNA), a unique causal-inference analytical framework that offers a holistic view of biological systems by integrating data from multiple cohorts and diverse omics types. TkNA helps to decipher key players and mechanisms governing host-microbiota (or any multi-omic data) interactions in specific conditions or diseases. TkNA reconstructs a network that represents a statistical model capturing the complex relationships between different omics in the biological system.

Manifestations of cruel, inhuman types of behavior and torture of Ukrainian military who died in captivity.

The given information and forensic medical characteristics of injuries found on the bodies of Ukrainian soldiers who were in Russian captivity and died as a result of cruel, inhuman treatment and torture in 2022-2023. According to their nature and morphological features, the damage could be the result of high temperature action using hot metal objects, but more likely, the result of the use of electric current conductors (bare end of the wire). In other cases, after the exhumation of the occupied territory of the Kharkiv region, the manifestations of torture were brain injuries and fractures of the bones of the body caused by blunt hard objects with a limited surface.

Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH.

Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome.

Background: The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice.

Transkingdom Network Analysis (TkNA): a systems framework for inferring causal factors underlying host-microbiota and other multi-omic interactions.

Technological advances have generated tremendous amounts of high-throughput omics data. Integrating data from multiple cohorts and diverse omics types from new and previously published studies can offer a holistic view of a biological system and aid in deciphering its critical players and key mechanisms. In this protocol, we describe how to use Transkingdom Network Analysis (TkNA), a unique causal-inference analytical framework that can perform meta-analysis of cohorts and detect master regulators among measured parameters that govern pathological or physiological responses of host-microbiota (or any multi-omic data) interactions in a particular condition or disease.

GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA.

Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats.

Introduction: In the present study, we aimed to test the hypothesis that hypercapnia, independently and/or in combination with hypoxia, can activate signaling pathways related to the inhibition of proapoptotic (caspase-dependent and caspase-independent) factors and the induction of antiapoptotic factors in facilitating adaptation to hypoxia/ischemia.

Materials And Methods: Following exposure to permissive hypercapnia and/or normobaric hypoxia, the degree of apoptosis was evaluated in experimental ischemia models in vivo and in vitro. The percentages of caspase-3, apoptosis-inducing factor (AIF), Bax, and Bcl-2 in astrocytes and neurons derived from male Wistar rats were also calculated.

Atmospheric Reactive Oxygen Species and Some Aspects of the Antiviral Protection at the Respiratory Epithelium.

The review summarizes literature data on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The special attention is paid to comprehensive analysis of up-to-date data on the activity of the lactoperoxidase system expressed on the surface of the respiratory epithelium which provides the generation of hypothiocyanate and hypoiodite in the presence of locally produced or inhaled hydrogen peroxide. Molecular mechanisms of production of active compounds with antiviral and antibacterial effects, expression profiles of enzymes, transporters and ion channels involved in the generation of hypothiocyanite and hypoiodite in the mucous membrane of the respiratory system in physiological and pathological conditions (inflammation) are discussed.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment.

The C-SHIFT Algorithm for Normalizing Covariances.

Omics technologies are powerful tools for analyzing patterns in gene expression data for thousands of genes. Due to a number of systematic variations in experiments, the raw gene expression data is often obfuscated by undesirable technical noises. Various normalization techniques were designed in an attempt to remove these non-biological errors prior to any statistical analysis.

Reproducibility of developmental neuroplasticity in brain tissue models.

The current prevalence of neurodevelopmental, neurodegenerative diseases, stroke and brain injury stimulates studies aimed to identify new molecular targets, to select the drug candidates, to complete the whole set of preclinical and clinical trials, and to implement new drugs into routine neurological practice. Establishment of protocols based on microfluidics, blood-brain barrier- or neurovascular unit-on-chip, and microphysiological systems allowed improving the barrier characteristics and analyzing the regulation of local microcirculation, angiogenesis, and neurogenesis. Reconstruction of key mechanisms of brain development and even some aspects of experience-driven brain plasticity would be helpful in the establishment of brain models with the highest degree of reliability.

Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.

Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use.

Molecular Mechanisms of Proteins - Targets for SARS-CoV-2 (Review).

Unlabelled: The rapidly accumulating information about the new coronavirus infection and the ambiguous results obtained by various authors necessitate further research aiming at prevention and treatment of this disease. At the moment, there is convincing evidence that the pathogen affects not only the respiratory but also the central nervous system (CNS). is to provide an insight into the molecular mechanisms underlying the damage to the CNS caused by the new coronavirus SARS-CoV-2.

[Atmospheric reactive oxygen species and some aspects of the antiviral protection of the respiratory epithelium].

The review focuses on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The authors provide a comprehensive analysis of up-to-date data on the activity of the lactoperoxidase system expressed on the surface of the respiratory epithelium which provides the generation of hypothiocyanate and hypoiodite in the presence of locally produced or inhaled hydrogen peroxide. Molecular mechanisms of production of active compounds with antiviral and antibacterial effects, expression profiles of enzymes, transporters and ion channels involved in the generation of hypothiocyanite and hypoiodate in the mucous membrane of the respiratory system in physiological and pathological conditions (inflammation) are discussed.

Blood-Brain Barrier Breakdown in Stress and Neurodegeneration: Biochemical Mechanisms and New Models for Translational Research.

Blood-brain barrier (BBB) is a structural and functional element of the neurovascular unit (NVU), which includes cells of neuronal, glial, and endothelial nature. The main functions of NVU include maintenance of the control of metabolism and chemical homeostasis in the brain tissue, ensuring adequate blood flow in active regions, regulation of neuroplasticity processes, which is realized through intercellular interactions under normal conditions, under stress, in neurodegeneration, neuroinfection, and neurodevelopmental diseases. Current versions of the BBB and NVU models, static and dynamic, have significantly expanded research capabilities, but a number of issues remain unresolved, in particular, personification of the models for a patient.

Hypercapnia Modulates the Activity of Adenosine A1 Receptors and mitoK-Channels in Rat Brain When Exposed to Intermittent Hypoxia.

The mechanisms and signaling pathways of the neuroprotective effects of hypercapnia and its combination with hypoxia are not studied sufficiently. The study aims to test the hypothesis of the potentiating effect of hypercapnia on the systems of adaptation to hypoxia, directly associated with A1-adenosine receptors and mitochondrial ATP-dependent K+ -channels (mitoK-channels). We evaluated the relative number of A1-adenosine receptors and mitoK-channels in astrocytes obtained from male Wistar rats exposed to various respiratory conditions (15 times of hypoxia and/or hypercapnia).

Neurogenic Potential of Implanted Neurospheres Is Regulated by Optogenetic Stimulation of Hippocampal Astrocytes Ex Vivo.

The protocol of optogenetic ChR2-mediated activation of astrocytes was used in a model of artificial neurogenic niche, neurospheres implanted into ex vivo organotypic cultures of mouse hippocampus. The electrophysiological characteristics of the hippocampus and expression of molecules involved in the mechanisms of activation of astrocytes and microglia (GFAP, CD38, C3/C3b, Cx43, CD11b, and CD18) were evaluated. Photoactivation of astrocytes led to activation of neurogenesis and changes in the expression of molecules (Cx43 and CD38) that determine bioavailability of NAD to ensure proliferative activity of cells in the neurogenic niche.

[Effect of sliding discharge on proliferation and death of brain microvessel endothelial cells in vitro].

The dose-dependent effects of plasma exposure to a unipolar nanosecond sliding discharge over the surface of the culture medium in a closed plate on the cells of cerebral endothelium in vitro were studied. Using a 24-well plate, the surface plasma energy density of one pulse was 360 μJ/cm2 at a pulse frequency of 100 Hz. It has been shown that in the creeping discharge plasma there is an active excitation of air molecules, the formation of positive nitrogen and oxygen ions, and the formation of carbon monoxide.

[Features of the in vitro expression profile of hippocampal neurogenic niche cells during optogenetic stimulation].

In the central nervous system of mammals, there are specialized areas in which neurogenesis - neurogenic niches - is observed in the postnatal period. It is believed that astrocytes in the composition of neurogenic niches play a significant role in the regulation of neurogenesis, and therefore they are considered as a promising "target" for the possible control of neurogenesis, including the use of optogenetics. In the framework of this work, we formed an in vitro model of a neurogenic niche, consisting of cerebral endothelial cells, astrocytes and neurospheres.