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The spiny mouse (Acomys species) is capable of scarless wound regeneration through largely yet unknown mechanisms. To investigate whether this capacity is related to peculiarities of the hemostatic system, we studied the blood of Acomys cahirinus in comparison to Mus musculus (Balb/c) to reveal differences in blood composition and clotting in both males and females. In response to surgical manipulations, blood clots formed in wounds of Acomys comprised a stronger hemostatic seal with reduced surgical bleeding in comparison with Balb/c. Acomys demonstrated notably shorter tail bleeding times and elevated clottable fibrinogen levels. Histological analysis revealed that clots from Acomys blood had densely packed fibrin-rich clots with pronounced fibrin segregation from erythrocytes. Acomys exhibited superior plasma clot stiffness as revealed with thromboelastography. The latter two characteristics are likely due to hyperfibrinogenemia. Light transmission platelet aggregometry demonstrated that ADP-induced platelet aggregates in Acomys males are stable, unlike the aggregates formed in the plasma of Balb/c undergoing progressive disaggregation over time. There were no apparent distinctions in platelet contractility and baseline expression of phosphatidylserine. Hematological profiling revealed a reduced erythrocytes count but increased mean corpuscular volume and hemoglobin content in Acomys. These results demonstrate the distinctive hemostatic potential of Acomys cahirinus, which may contribute to their remarkable regenerative capacity. [ABSTRACT FROM AUTHOR]

In mammals, cartilage tissue has a low potential for regeneration. Typically, the defect site is replaced by connective tissue. The Acomys cahirinus mouse is a relatively new model for studying tissue regeneration processes, specifically the elastic cartilage of the auricle. To investigate the molecular genetic mechanisms responsible for these processes and gain insight into the cellular and tissue composition of the intact auricle, we utilized the method of single-cell RNA sequencing (scRNA-seq). This method enables quantification of gene expression in the sample and modeling of cell clustering based on expression profiles. This allows for assessment of sample heterogeneity in terms of specific cell populations. Annotation of cell types, particularly in non-model organisms, should be supported by classical morphological studies to allow for more detailed identification of cell populations. This is necessary to separate clusters of cells that are grouped statistically on the basis of similar expression profiles of a group of genes into smaller subpopulations. The objective of this study was to annotate all cell types present in the intact Acomys cahirinus auricle using a combination of transcriptomic approaches and classical methods of histology. The study resulted in the annotation of 24 cell clusters based on known marker genes and by comparing genetic and morphological data. [ABSTRACT FROM AUTHOR]

The study of adrenal disorders is a key component of scientific research, driven by the complex innervation, unique structure, and essential functions of the adrenal glands. This review explores the use of non-traditional animal models for studying congenital adrenal hyperplasia. It highlights the advantages, limitations, and relevance of these models, including domestic ferrets, dogs, guinea pigs, golden hamsters, pigs, and spiny mice. We provide a detailed analysis of the histological structure, steroidogenesis pathways, and genetic characteristics of these animal models. The morphological and functional similarities between the adrenal glands of spiny mice and humans highlight their potential as an important avenue for future research. [ABSTRACT FROM AUTHOR]

Using the polymerization filling technique, composite materials have been obtained based on ultra-high molecular weight PE and fillers of platelike (graphene or graphite nanoplatelets) and spherical (silica) types. The tensile stress–strain characteristics of samples obtained using different pressing modes have been examined. It has been revealed that the cooling rate of the samples during pressing affects the values of ultimate tensile strength and modulus of elasticity in tension. The characteristics of composites processed at a low cooling rate (10 K/h) are 30% higher than those of the samples obtained at a high cooling rate (10 K/min). Using DSC, DMA, and X-ray diffraction methods, it has been shown that the way of cooling affects the crystallite size of compressed samples of composite materials. [ABSTRACT FROM AUTHOR]

Postnatal islets of Langerhans retain cellular elements that have a several stem cell markers. It can be supposed that islet cells are not a static population and they can give rise to the new endocrinocytes. The aim of our work was to study the proliferative capacity of pancreatic islet cells and their subsequent differentiation in the late prenatal, early postnatal, and adult periods of human ontogenesis. A study of the late perinatal development of the human pancreas was performed on a sample resulting of legal medical abortion with the voluntary consent of the mother (30 weeks gestation), autopsy of the infant pancreas (from 17 days to 2 months after the birth) and adult pancreas (38–66 years old). Pancreas paraffin sections were stained immunohistochemically with commercial antibodies to insulin, Ki-67 (marker of proliferation), glucagon, and C-kit (stem and progenitor cell marker). It was found that proliferating cells remain in human pancreatic islets up to at least 2 months after the birth, the number of which can be up to 3.5% of islet cells. Some of these cells can synthesize glucagon. Based on the obtained results, we suppose that the cells of Langerhans islet are not a constant or static cells population. After the birth, there are cells in the islet which are capable to proliferate and differentiate. Because endocrinocyte differentiation into β-cells goes through the stage of glucagon-producing cells, it is possible that the origin of diabetes mellitus type I may be associated with the disturbance of proliferation and differentiation of the islet of Langerhans cells and a population imbalance between already differentiated α and β-cells. [ABSTRACT FROM AUTHOR]

Hölder matrix functions of the second order are considered. We assume that one element is arbitrary, diagonal elements do not vanish on the contour, and the choice of the last element determines the possibility of their effective factorization. [ABSTRACT FROM AUTHOR]

A number of sarcolemma proteins are responsible for muscle fiber repair. Dysferlin encoded by the DYSF gene is one of these proteins. Dysferlin promotes membrane repair in striated muscle fibers (MFs). Mutations in DYSF lead to loss of or decreased dysferlin expression, impaired membrane repair in MF, and its destruction, clinically manifesting as dysferlinopathy. Preclinical studies of cell and gene therapies aimed at restoring impaired muscle regeneration require well-characterized small animal models. Our investigation aimed to distinguish the histopathological features of a mouse strain lacking dysferlin expression (Bla/J strain). Ultrastructural changes in the sarcolemma, mitochondria and contractile apparatus were observed. It was shown that postnatal histogenesis of skeletal muscles in genetically determined dysferlin deficiency is characterized by a higher proportion of necrotic muscle fibers, compensatory hypertrophy of muscle fibers with their subsequent atrophy, and decreases in proliferative activity and the level of myogenic differentiation of myogenic progenitor cells compared to wild-type mice (C57Bl/6). [ABSTRACT FROM AUTHOR]

We evaluated intestinal permeability in primary biliary cholangitis (PBC) in our study. Overall, 41 people were included in the cross-sectional study. Intestinal permeability was assessed in 20 patients with PBC and 21 healthy volunteers. Healthy volunteers without a history of liver disease do not drink alcohol and are with normal analysis. Patients' age is 18 years and above given a diagnosis of PBC based on actual recommendations—EASL (2017). Small intestine permeability was evaluated by ratio of lactulose/mannitol in urine and large bowel permeability was evaluated by level of sucralose in urine (nmol/l), using the method of high-performance liquid chromatography–mass spectrometry. All patients with PBC had increased ratio of lactulose/mannitol (0.106 [0.07; 0.22]; p < 0.001) compared with the control group (0.013 [0.01; 0.025]); level of sucralose was not changed. Patients with PBC with portal hypertension had increased both small intestine permeability (0.076 [0.036; 0.23]; p < 0.05) and large bowel permeability (1091.2 [480; 2176]; p < 0.001) compared with the control group (785.6 [408; 1027.2]). [ABSTRACT FROM AUTHOR]

Serum cytokine levels were explored in patients with primary biliary cholangitis. Eighteen patients with primary biliary cholangitis were included in the cross-sectional study. Serum cytokine levels were measured at baseline and compared to those of 21 healthy individuals. Patients with primary biliary cholangitis had significantly higher levels of cytokines — IL (interleukin) − 6 0.7 [0.34; 0.87] (p < 0.001), IL-8 1.5 [0.85; 2.8] (p < 0.001), and TNF-α (tumor necrosis factor-α) 3.5 [2.5; 6.5] (p < 0.001) compared with the control group IL-6 0.4 [0.31; 0.51], IL-8 0.53 [0.44; 0.67], and TNF-α 1.65 [1.33; 1.95]. Adjusted logistic regression analysis revealed a pronounced relation of IL-8 and primary biliary cholangitis — 16.148 (1.86–139.65). The association between the level of other cytokines and primary biliary cholangitis was assessed as nonsignificant. In the language of absolute numbers, the increase of IL-8 serum level by 1 pg/ml had increased the chance for a patient to find himself in a group of primary biliary cholangitis by 16.148 times. In addition, high IL-8 serum levels were strongly related to laboratory variables (AST (Aspartate aminotransferase), Alkp (alkaline phosphatase), ERS (erythrocyte sedimentation rate), Albumin). [ABSTRACT FROM AUTHOR]

The study assessed reactivity of stromal-vascular skeletal muscle differons to acute chemical injury. Dysferlin-deficient Bla/J mice and the wild-type С57BL/6 mice were intramuscularly injected with 100 μl of 0.5% procaine solution. The middle segment of gastrocnemius muscle was taken on postsurgery days 2, 4, 10, and 14 for routine histological examination. To evaluate proliferation and vascularization, the paraffin sections were stained immunohistochemically with antibodies to α-smooth muscle actin and Ki-67. The connective tissue was stained according to Mallory. The study revealed diminished proliferative activity of stromal-vascular differons and decreased vascular density in muscles of Bla/J mice. Thus, mutations in the DYSF gene coding dysferlin down-regulate the reparation processes in all differons of skeletal muscle. [ABSTRACT FROM AUTHOR]

We consider a three-dimensional Riemann boundary value problem which has two particular solutions such that, for one of the components, the ratios of the boundary values coincide on the conjugation contour. It is shown that, under certain restrictions on the elements of the matrix coefficient of the problem, its general solution can be obtained in a closed form. [ABSTRACT FROM AUTHOR]

We show that if a three-dimensional linear conjugation problem has two particular solutions with coinciding ratios of boundary values of two their components, then its general solution can be obtained in closed form. [ABSTRACT FROM AUTHOR]

An adequate experimental model is important to understand pathophysiological processes ongoing in the pancreas with diabetes mellitus. Our study was aimed to describe early ultra- and microstructural changes in the rat pancreas in 12–48 h after alloxan administration in a dose of 180 mg/kg. A histopathological examination of the endocrine pancreas revealed the loss of borders between endocrine cells, granular dystrophy and degranulation, sings of necrosis in central cells of the Langerhans islets and apoptosis of their peripheral ones manifested as DNA fragmentation and an increased expression of apoptosis markers. There was a gradual increase of a Langerhans islet area, a decreased percentage of insulin+ cells and an increased one of glucagon+ cells, as well as the presence of proliferating islet cells were found. Structural changes of the exocrine pancreas included fatty degeneration, signs of exocrine cell mitochondrial damage, increased acini, which are located mainly around the Langerhans islets, as well as perivascular edema and leukocytic infiltration. Described ultra- and microstructural alterations suggest a significant contribution of apoptosis to death of endocrine cells exposed to alloxan. Coexisting damage of the exocrine pancreas with its stroma involvement is for the first time described. [ABSTRACT FROM AUTHOR]

We consider the structure of the set of piecewise meromorphic solutions of a homogeneous linear conjugation problem for a four-dimensional vector. We show that in the presence of three piecewise meromorphic solutions to the linear conjugation problem it is possible to construct a canonical system of solutions to the linear conjugation problem and distinguish some classes of problems that are solvable in closed form. [ABSTRACT FROM AUTHOR]

Perineuronal net (PNN) is a highly structured portion of the CNS extracellular matrix (ECM) regulating synaptic plasticity and a range of pathologic conditions including posttraumatic regeneration and epilepsy. Here we studied Wisteria floribunda agglutinin-stained histological sections to quantify the PNN size and enrichment of chondroitin sulfates in mouse brain and spinal cord. Somatosensory cortex sections were examined during the period of PNN establishment at postnatal days 14, 21 and 28. The single cell PNN size and the chondroitin sulfate intensity were quantified for all cortex layers and specifically for the cortical layer IV which has the highest density of PNN-positive neurons. We demonstrate that the chondroitin sulfate proteoglycan staining intensity is increased between P14 and P28 while the PNN size remains unchanged. We then addressed posttraumatic changes of the PNN expression in laminae 6 and 7 of cervical spinal cord following hemisection injury. We demonstrate increase of the chondroitin sulfate content at 1.6–1.8 mm rostrally from the injury site and increase of the density of PNN-bearing cells at 0.4–1.2 mm caudally from the injury site. We further demonstrate decrease of the single cell PNN area at 0.2 mm caudally from the injury site suggesting that the PNN ECM takes part in the posttraumatic tissue rearrangement in the spinal cord. Our results demonstrate new insights on the PNN structure dynamics in the developing and posttraumatic CNS. [ABSTRACT FROM AUTHOR]

Herein we present a clinical case of the Caroli syndrome caused by the compound heterozygous mutation in the PKHD1 gene. Histopathological assessment of liver detected biliary cirrhosis, numerous dilated bile ducts of various sizes, hyperplastic cholangiocytes containing a large amount of acid mucopolysaccharides, decreased ß-tubulin expression and increased proliferation of cholangiocytes. A significant proportion of hepatic tissue was composed of giant cysts lined with a single layer of cholangiocytes, containing pus and bile in its lumen and surrounded by granulation tissue. An accumulation of neutrophils in the lumen of the bile ducts was observed, as well as an infiltration of the ducts and cysts surrounding connective tissue by CD4+ and to a lesser extent CD8+ lymphocytes. This may be caused by the expression of HLA-DR by cholangiocytes. Atrophy and desquamation of the epithelium of collecting tubules with the formation of microcysts were detected in the kidneys without a clinically significant loss of renal function. Morphopathogenetic mechanisms of the Caroli syndrome can be targets for a potential pathogenetic therapy and prevention of its manifestations and complications. [ABSTRACT FROM AUTHOR]

This clinical study describes the intralesional application of the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor (VEGF164) and fibroblast growth factor 2 (FGF2) in seven horses to restore naturally occurring injuries of the superficial digital flexor tendon (SDFT) (tendinitis) and in three horses with suspensory ligament branch desmitis. Following application all horses were able to commence a more rapid exercise program in comparison to standardized exercise programs. Clinical observation and ultrasonic imaging was used to evaluate the regeneration rate of the tendon and ligament injury recovery and to confirm the safety of this gene therapy in horses, throughout a 12 month period. Follow-up data of the horses revealed a positive outcome including significant ultrasonographic and clinical improvements in 8 out of 10 horses with SDFT and suspensory ligament branch lesions, with return to their pre-injury level of performance by 2–6 months after the completion of treatment. The ninth horse initially presenting with severe suspensory ligament branch desmopathy, showed no significant ultrasonographic improvements in the first 2 months after treatment, however, it improved clinically and became less lame. The final horse, presenting with severe tendinitis of the SDFT returned to their pre-injury level of performance, but experienced re-injury 6 months after treatment. This data is highly promising, however, further research in experimental models, with the histopathological, immunohistochemical and gene expression evaluation of the equine tendon/ligament after gene therapy application is required in order to fully understand the mechanisms of action. This treatment and the significant clinical impacts observed represents an important advancement in the field of medicine. [ABSTRACT FROM AUTHOR]

Since the 1990s, when it was demonstrated by Hammel and others that liver fibrosis is reversible, researchers and physicians actively search for new antifibrotic therapies. In recent years, knowledge of liver fibrosis pathophysiology has greatly advanced and new cellular and molecular mechanisms were described. The cells that determine extracellular matrix components distribution are myofibroblasts, but their origin is diverse. They can be activated hepatic stellate cells (HSCs), portal fibroblasts (PF), or circulating mesenchymal stem cells of the bone marrow. Among large number of substrates to inhibit activation, to inhibit proliferation of myofibroblasts, and to induce their apoptosis we, chose curcumin and gliotoxin. Primarily, in the current work, we optimized the explantation culture method for isolation of hepatic myofibroblasts and received two different cultures—myofibroblasts of HSC and PF origin. Exposition of 50 μM curcumin and 0.1 μM gliotoxin was the most optimal; we observed suppression of hepatic myofibroblast activation and inhibition of their proliferation. These results extend the current knowledge of the cells within the liver fibrogenic populations and prove inhibitory influence of biologically active substances (curcumin and gliotoxin) on portal myofibroblasts. [ABSTRACT FROM AUTHOR]

Establishing an analogy between the theories of Riemann-Hilbert vector problem and linear ODEs, for the n-dimensional homogeneous linear conjugation problem on a simple smooth closed contour Γ partitioning the complex plane into two domains D+ and D− we show that if we know n−1 particular solutions such that the determinant of the size n−1 matrix of their components omitting those with index k is nonvanishing on D+ ∪ Γ and the determinant of the matrix of their components omitting those with index j is nonvanishing on Γ ∪ D− {∞}, where k,j=1,n¯, then the canonical system of solutions to the linear conjugation problem can be constructed in closed form. [ABSTRACT FROM AUTHOR]

The notion of approximate factorization of a Hölder matrix function on a simple smooth closed contour is introduced. The elements of a (2 × 2)-matrix function of a special form are approximated by polynomials in z and 1/ z. Sufficient conditions for the vanishing of the partial indices of the approximating matrix function are found. Factorization of the approximating matrix function is explicitly constructed. [ABSTRACT FROM AUTHOR]

Human tooth germ stem cells (hTGSCs) originate from the neural crest and have a great potential to be used in stem cell therapies. Our group has previously shown that Pluronics interact with stem cells and affect their biological function. Pluronics block copolymer (P85), a potential drug delivery agent in the micelle form, which was shown to improve stem cell expansion. However, it is not known how P85 treatment affects the transcription profile of hTGSCs. In the present study, we found substantial changes in the expression of 252 genes in response to P85 treatment by using Illumina microarray. The gene enrichment was carried out using database for annotation, visualization, and integrated discovery (DAVID) and the results classified in several biologically meaningful clusters. Using bioinformatics tools, we constructed a global regulatory network of P85-modulated genes associated with stem cell differentiation pathways and multi-drug resistance (MDR) processes. In conclusion, our results were compatible with many of the P85-mediated biological processes and may help us to gain a better molecular understanding of P85 biological function. [ABSTRACT FROM AUTHOR]

We offer a method for building a canonical system of solutions of a linear conjugation problem for two-dimensional vector in the case where one of its solution is known. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves. [ABSTRACT FROM AUTHOR]

C-kit—a stem cell receptor, or CD117, is one of the markers of human pancreatic endocrinocyte progenitor cells. Its important role in the proliferation and differentiation of pancreatic endocrine cells during human prenatal development has already been proven. However, the presence and role of c-kit-positive cells in adult pancreatic islets remains unclear. The purpose of our study was to establish the presence of c-kit-positive cells in the adult pancreatic islets and to assess whether they retain the ability to proliferate during a lifetime. We studied pancreatic autopsies of adults aged 50 to 70 years, which were obtained in pathology departments of Kazan hospitals. Samples of the pancreas were embedded in paraffin using standard techniques. Paraffin sections of the pancreas were stained immunohistochemically with commercial antibodies against c-kit, insulin, glucagon, and Ki-67. Few c-kit-positive cells simultaneously secreting insulin or glucagon were detected in all samples studied. These data suggest that such cells are in a state of differentiation into endocrinocytes, but no proliferation of c-kit-positive cells was observed. [ABSTRACT FROM AUTHOR]

Mental illnesses are frequent co-morbid conditions in chronic systemic diseases. High incidences of depression, anxiety and cognitive impairment complicate cardiovascular and metabolic disorders such as hypertension and diabetes mellitus. Lifestyle changes including regular exercise have been advocated to reduce blood pressure and improve glycaemic control. The purpose of this project was to evaluate the effect of physical training on the most prevalent corollary psychiatric problems in patients with chronic organic ailments. This longitudinal study assessed the mental health of hypertensive (age: 57 ± 8 years) and/or diabetic (age: 53 ± 8 years) patients using mini-mental state examination, Beck’s depression inventory, Beck’s anxiety inventory and self-reporting questionnaire-20 before and after a 3-month supervised resistance and aerobic exercise programme comprising structured physical activity three times a week. Clinically relevant improvement was observed in the Beck’s depression inventory and Beck’s anxiety inventory scores following the 12-week training (61%, p = 0.001, and 53%, p = 0.02, respectively). Even though statistically not significant (p = 0.398), the cognitive performance of this relatively young patient population also benefited from the programme. These results demonstrate positive effects of active lifestyle on non-psychotic mental disorders in patients with chronic systemic diseases, recommending exercise as an alternative treatment option. [ABSTRACT FROM AUTHOR]

We consider structure of the set of piecewise-meromorphic solutions of the homogeneouslinear conjugation problems for three-dimensional vector, and study their relations with a system of two problems of fractional-linear conjugation. The main result of the paper is the following one: known two piecewise-meromorphic solutions of the system, we are able to construct a canonical system of solutions to the linear conjugation problem and to separate a class of problems resolvable in closed form [ABSTRACT FROM AUTHOR]

We consider the structure of the set of piecewise meromorphic solutions for a homogeneous linear conjugation problem for a three-dimensional vector. We show that, in the presence of two piecewise meromorphic solutions to the linear conjugation problem, it is possible to construct a canonical system of solutions to the linear conjugation problem and distinguish some classes of problems solvable in closed form. [ABSTRACT FROM AUTHOR]

Peripheral arterial diseases are characterized by a progressing tissue ischemia which results in the invalidization of patients. The aim of our research was to study the morphological effects of autologous peripheral blood stem cells intramuscular injection into patients with peripheral arterial disease. Peripheral blood stem cells were transplanted intramuscularly into a 48-year-old male patient with peripheral arterial disease stage IIb by Fontaine. The biopsies of his gastrocnemius muscle were taken before the stem cells were transplanted and 3 months after transplantation. These biopsies were stained with H&E and also with antibodies against CD34, myogenin, caspase 3, and bcl-2. Immunohistochemical study results showed an increase of capillary density of 32.7 % ( P = 0.005). In muscular biopsies obtained before therapy, we identified single myogenin+ myosatellite cells, while 3 months after transplantation we detected the presence of cells with myogenin-positive nuclei and multinucleated myotubes. We also observed the formation of young myogenin+ muscle fibers with central nuclei. There was no significant difference in the expression of caspase-3 before transplantation and 3 months after transplantation. An increased number of bcl-2+ myosatellite cells, myotubes, and muscle fibers were detected after transplantation. The patient's ankle-brachial index increased by 13.56 % (0.59 before and 0.67 3 months post transplantation). The patient's pain-free walking distance by 89.97 % (from 59.56 to 113.77 m). Control arteriograms showed the formation of new collaterals. Transplanted autologous peripheral blood stem cells stimulated the formation of new capillaries, the activation of myosatellite cells and bcl-2 expression in muscle fibers. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by progressive death of cerebral and spinal motorneurons. Using behavioral tests we studied the efficiency of gene-cell therapy in SOD1 G93A transgenic mice receiving xenotransplantation of human umbilical cord blood mononuclear cells genetically modified with adenoviral vectors encoding vascular endothelial growth factor (VEGF) and reporter green fluorescent protein (EGFP) genes. The cells were transplanted to mice on week 27 of life (preclinical stage of the disease). Behavioral tests (open field, grip strength test) showed that transplantation of umbilical cord blood mononuclear cells expressing VEGF significantly improved the parameters of motor and explorative activity, grip strength, and animal survival. Thus, gene-cell therapy based on genetically modified mononuclear cells expressing VEGF can be efficient for the treatment of amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

We consider the structure of the set of piecewise meromorphic solutions to the linear conjugation problem for a two-dimensional vector and study its relations with the fractional-linear conjugation problem. We prove that under the assumption of the piecewise meromorphic solvability of any of these problems there exists a canonical system of solutions to the linear conjugation problem and describe classes of problems which are solvable in a closed form. [ABSTRACT FROM AUTHOR]

We obtain sufficient conditions for the factorization of second-order matrix functions in the closed form. [ABSTRACT FROM AUTHOR]

The presence of several subtypes of P2X receptors on early hemopoietic precursors (CD34) from human umbilical blood was detected by flow cytometry. The expression of P2X receptors on umbilical blood lymphocytes was an order of magnitude higher than that on adult human blood cells. Our results attest to early involvement of P2X receptors in differentiation of human hemopoietic cells. [ABSTRACT FROM AUTHOR]

We consider the characteristic system of singular integral equations for two unknown functions. We obtain certain correlations connecting coefficients of the system which allow one to solve the latter in a closed form. Based on the obtained results, we consider cases of the solvability in a closed form for one class of singular integral equations. [ABSTRACT FROM AUTHOR]

Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's type dementia is proposed. [ABSTRACT FROM AUTHOR]

Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's-type dementia is proposed. [ABSTRACT FROM AUTHOR]

Abstract  The study has been carried out to verify the authors’ hypothesis that degeneration of dopaminergic (DA-ergic) neurons of the hypothalamic tuberoinfundibular system and concomitant development of hyperprolactinemia are accompanied by involvement of compensatory synthesis of dopamine (DA) by non-dopaminergic neurons expressing single complementary enzymes of synthesis of this neurotransmitter. Degeneration of DA-ergic neurons was produced by a stereotaxic injection into the brain lateral ventricles of 6-hydroxydopamine (6-HDA)—a specific neurotoxin of DA-ergic neurons. 14 and 45 days after the toxin administration there were determined concentration of prolactine in peripheral blood by methods of immunoenzyme and radioimmunological analyses as well as the DA amount in the arcuate nucleus by the method of highly efficient liquid chromatography with electrochemical detection. In a part of the animals, sections were prepared from the mediobasal hypothalamus (arcuate nucleus and medial eminence) and perfused with Krebs—Ringer medium; then the DA concentration was determined in the sections and in the incubation medium. 14 days after the neurotoxin administration there were revealed an increase of blood prolactine concentration and a decrease of DA concentration in the arcuate nucleus in vivo as well a decrease of the total DA amount in the sections and incubation medium in experiments in vitro. 45 days after the neurotoxin administration, all the above parameters returned to the normal level. Thus, the obtained data indicate that the hyperlactinemia and DA deficit appearing during degeneration of the arcuate nucleus DA-ergic neurons seem to be compensated due to an enhancement of DA synthesis by non-dopaminergic monoenzyme neurons of arcuate nucleus. [ABSTRACT FROM AUTHOR]

Cultured pure population of Ito cells isolated from adult rat liver expressed epithelial markers cytokeratin-8, α-fetoprotein, and γ-glutamyl transpeptidase after forming a dense monolayer. Mesenchymal-epithelial transformation of these cells is possible, which suggests them as candidates of hepatic stem cells. [ABSTRACT FROM AUTHOR]

Dimephosphone injected on days 1-19 of gestation did not cause fetal death and specific abnormalities in rats and did not modulate sex differentiation of fetuses. Morphological study of fetal liver revealed no pathological changes. [ABSTRACT FROM AUTHOR]

The effect of Gram-negative bacterial lipopolysaccharide on rat hepatocytes and sinusoidal cells was studied. The damage and regeneration potential of the liver were evaluated by activation of perisinusoidal Ito cells and proliferative activity of liver cells. Compensatory and repair reactions in the liver induced by lipopolysaccharide manifested by proliferation of liver cells and reversible activation of Ito cells without their transdifferentiation into myofibroblasts. [ABSTRACT FROM AUTHOR]

The effect of Gram-negative bacterial lipopolysaccharide on rat hepatocytes and sinusoidal cells was studied. The damage and regeneration potential of the liver were evaluated by activation of perisinusoidal Ito cells and proliferative activity of liver cells. Compensatory and repair reactions in the liver induced by lipopolysaccharide manifested by proliferation of liver cells and reversible activation of Ito cells without their transdifferentiation into myofibroblasts. [ABSTRACT FROM AUTHOR]

Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses' furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases. [ABSTRACT FROM AUTHOR]

We evaluated the relationship between pathological changes in the liver and the state of intestinal microflora in rats with experimental dysbiosis. Changes in the intestinal microflora were accompanied by alteration of the morphological structure in the liver. Enhanced proliferation of Ito cells served as an indirect evidence of damage to the liver. Ito cells did not undergo transformation into myofibroblasts that excluded the possibility of fibrosis. [ABSTRACT FROM AUTHOR]

Isolated human hepatocytes cultured in liver biomatrix express cytokeratins 8 and 18. By the end of the first and during the second week in culture, hepatocytes, express these cytokeratins and react with antibodies to cytokeratin-19. Cytokeratin-7 was found in individual cholangiocytes contaminating the culture. The presence of cytokeratin-19 in hepatocytes during the second week of culturing can be regarded as its reexpression. [ABSTRACT FROM AUTHOR]