Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats.

Normotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of the hypothalamus of hypertensive ISIAH rats, modeling a stress-sensitive form of arterial hypertension, and normotensive WAG rats at rest and after exposure to a single short-term restraint stress. It was shown that oxidative phosphorylation is the most significantly enriched process among metabolic changes in the hypothalamus of rats of both strains when exposed to a single short-term restraint stress.

[Restraint Stress-Induced Expression of Fos and Several Related Genes in the Hypothalamus of Hypertensive ISIAH Rats].

Stress can play a significant role in arterial hypertension and many other complications of cardiovascular diseases. Considerable attention is paid to the study of the molecular mechanisms involved in the body response to stressful influences, but there are still many blank spots in understanding the details. ISIAH rats model the stress-sensitive form of arterial hypertension.

Effect of Short-Term Restraint Stress on the Hypothalamic Transcriptome Profiles of Rats with Inherited Stress-Induced Arterial Hypertension (ISIAH) and Normotensive Wistar Albino Glaxo (WAG) Rats.

Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h).

Collagen organization and structure in mice using label-free microscopy: implications for pelvic organ prolapse.

Pelvic organ prolapse (POP) is a gynecological disorder described by the descent of superior pelvic organs into or out of the vagina as a consequence of disrupted muscles and tissue. A thorough understanding of the etiology of POP is limited by the availability of clinically relevant samples, restricting longitudinal POP studies on soft-tissue biomechanics and structure to POP-induced models such as fibulin-5 knockout ( ) mice. Despite being a principal constituent in the extracellular matrix, little is known about structural perturbations to collagen networks in the mouse cervix.

A Principal Components Analysis and Functional Annotation of Differentially Expressed Genes in Brain Regions of Gray Rats Selected for Tame or Aggressive Behavior.

The process of domestication, despite its short duration as it compared with the time scale of the natural evolutionary process, has caused rapid and substantial changes in the phenotype of domestic animal species. Nonetheless, the genetic mechanisms underlying these changes remain poorly understood. The present study deals with an analysis of the transcriptomes from four brain regions of gray rats (), serving as an experimental model object of domestication.

Improved cancer risk stratification of isoechoic thyroid nodules to reduce unnecessary biopsies using quantitative ultrasound.

Objective: Gray-scale ultrasound (US) is the standard-of-care for evaluating thyroid nodules (TNs). However, the performance is better for the identification of hypoechoic malignant TNs (such as classic papillary thyroid cancer) than isoechoic malignant TNs. Quantitative ultrasound (QUS) utilizes information from raw ultrasonic radiofrequency (RF) echo signal to assess properties of tissue microarchitecture.

Collagen organization and structure in mice using label-free microscopy: implications for pelvic organ prolapse.

Pelvic organ prolapse (POP) is a gynecological disorder described by the descent of superior pelvic organs into or out of the vagina as a consequence of disrupted muscles and tissue. A thorough understanding of the etiology of POP is limited by the availability of clinically relevant samples, restricting longitudinal POP studies on soft-tissue biomechanics and structure to POP-induced models such as fibulin-5 knockout () mice. Despite being a principal constituent in the extracellular matrix, little is known about structural perturbations to collagen networks in the mouse cervix.

RatDEGdb: a knowledge base of differentially expressed genes in the rat as a model object in biomedical research.

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers.

Metabolic profile of blood serum in experimental arterial hypertension.

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans.

Animal Models of Hypertension (ISIAH Rats), Catatonia (GC Rats), and Audiogenic Epilepsy (PM Rats) Developed by Breeding.

Research into genetic and physiological mechanisms of widespread disorders such as arterial hypertension as well as neuropsychiatric and other human diseases is urgently needed in academic and practical medicine and in the field of biology. Nevertheless, such studies have many limitations and pose difficulties that can be overcome by using animal models. To date, for the purposes of creating animal models of human pathologies, several approaches have been used: pharmacological/chemical intervention; surgical procedures; genetic technologies for creating transgenic animals, knockouts, or knockdowns; and breeding.

Age-Dependent Changes in the Relationships between Traits Associated with the Pathogenesis of Stress-Sensitive Hypertension in ISIAH Rats.

Hypertension is one of the most significant risk factors for many cardiovascular diseases. At different stages of hypertension development, various pathophysiological processes can play a key role in the manifestation of the hypertensive phenotype and of comorbid conditions. Accordingly, it is thought that when diagnosing and choosing a strategy for treating hypertension, it is necessary to take into account age, the stage of disorder development, comorbidities, and effects of emotional-psychosocial factors.

Hypotensive Effects of Arginase Inhibition by L-Norvaline in Genetic Models of Normotensive and Hypertensive Rats.

The main effect of arginase inhibition after administration of L-norvaline is a decrease in BP. At the same time, norvaline causes various side effects in normotensive and hypertensive animals. In our experiments, L-norvaline was administered intraperitoneally (30 mg/kg) for 7 days to normotensive WAG rats (Wistar Albino Glaxo) and hypertensive ISIAH rats (Inherited, Stress-Induced Arterial Hypertension).

[Genes Associated with Increased Stress Sensitivity in Hypertensive ISIAH Rats].

Inherited stress-induced arterial hypertension (ISIAH) rats are characterized by increased stress reactivity of the hypothalamic-pituitary-adrenal and sympathoadrenal systems. The genetic basis of increased susceptibility to stress was studied in hypertensive ISIAH rats. Adrenal transcriptomes were sequenced in hypertensive ISIAH and normotensive WAG rats, and nine differentially expressed genes (DEGs) were found in the X-chromosome locus that was previously associated with mild emotional stress-induced increases in blood pressure and plasma corticosterone and an increased adrenal weight in ISIAH rats.

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells.

Glucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy.

Identification of Hypothalamic Long Noncoding RNAs Associated with Hypertension and the Behavior/Neurological Phenotype of Hypertensive ISIAH Rats.

Long noncoding RNAs (lncRNAs) play an important role in the control of many physiological and pathophysiological processes, including the development of hypertension and other cardiovascular diseases. Nonetheless, the understanding of the regulatory function of many lncRNAs is still incomplete. This work is a continuation of our earlier study on the sequencing of hypothalamic transcriptomes of hypertensive ISIAH rats and control normotensive WAG rats.

Biocoating-A Critical Step Governing the Oral Delivery of Polymeric Nanoparticles.

Decades of research into the topic of oral nanoparticle (NP) delivery has still not provided a clear consensus regarding which properties produce an effective oral drug delivery system. The surface properties-charge and bioadhesiveness-as well as in vitro and in vivo correlation seem to generate the greatest number of disagreements within the field. Herein, a mechanism underlying the in vivo behavior of NPs is proposed, which bridges the gaps between these disagreements.

CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development.

Intercellular communication orchestrates a multitude of physiologic and pathologic conditions. Algorithms to infer cell-cell communication and predict downstream signalling and regulatory networks are needed to illuminate mechanisms of stem cell differentiation and tissue development. Here, to fill this gap, we developed and applied CellComm to investigate how the aorta-gonad-mesonephros microenvironment dictates haematopoietic stem and progenitor cell emergence.

Domestication Explains Two-Thirds of Differential-Gene-Expression Variance between Domestic and Wild Animals; The Remaining One-Third Reflects Intraspecific and Interspecific Variation.

Belyaev's concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before human testing.

mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs).

Hypothalamic Norepinephrine Concentration and Heart Mass in Hypertensive ISIAH Rats Are Associated with a Genetic Locus on Chromosome 18.

The relationship between activation of the sympathetic nervous system and cardiac hypertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension.

Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4 mouse model of PFIC3.

Background & Aims: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation.

Methods: We have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs).