bluuebunny/crossref_metadata_2025 huggingface dataset:
Recintos y ajuar eclesiástico entre Chiapas y Guatemala. Una mirada documental diocesana a los Zendales y la Guardianía de Huitiupán
Authors: Sigaut Nelly
Published: October 2024

Es un recorrido de imágenes y una amplia investigación de textos obtenidos del Fondo Diocesano del Archivo Histórico Diocesano de San Cristóbal de las Casas.
Territorios violados. Indios, Medio ambiente y desarrollo en América Latina
Authors: Maldonado Alvarado Benjamín
Published: October 2024

Resultado de una investigación realizada a principios de la década de 1990, la problemática que plantea es vigente. Una fuerte crítica al extractivismo, por el feroz saqueo y descuido de la conservación ecológica en territorios indígenas de Brasil y el Istmo de Tehuantepec.
Sustainable Water Management Solutions for Urban Areas
Authors: Mohsin Md.
Published: October 2024

The management of water resources is a serious concern in urban areas because of the effects of climate change, aging infrastructure, and rapid population increase. This essay examines the vital significance of sustainable water management in urban settings, emphasizing cutting-edge frameworks for policy and technology that can improve water resilience and efficiency. Successful strategies, such as demand management and diversification of the water supply, are demonstrated by case studies like Windhoek, Namibia. In order to solve the intricate and interrelated problems of urban water scarcity, infrastructure constraints, and environmental repercussions, the essay emphasizes integrated water resources management (IWRM) as a crucial technique that incorporates multidisciplinary viewpoints. In order to guarantee a sustainable urban water future, the importance of inclusive policies and governance is also covered, highlighting the necessity of cooperative and flexible problemsolving techniques.
Relaciones temporales en construcciones absolutas de gerundio
Authors: Trebisacce Romina , Polakof Ana
Published: October 2024

El objetivo de este trabajo es explorar de qué modo se codifican las relaciones temporales en las construcciones absolutas de gerundio y, al mismo tiempo, presentar un modelo semántico que dé cuenta de este fenómeno de un modo explícito. En concreto, este trabajo presentará evidencias en favor de la hipótesis de que la información aspectual contenida en las construcciones absolutas de gerundio permite “resolver” las relaciones temporales. Partimos de la hipótesis central de Portner para el estudio de las construcciones absolutas del inglés, que supone una relación R que permite establecer relaciones temporales entre la construcción de gerundio y la cláusula principal. Sin embargo, a diferencia de su propuesta, en el que la relación R se especifica a partir de las relaciones entre la construcción absoluta y la oración principal, aquí sostenemos que esta relación temporal se especifica a partir del aspecto léxico del predicado de la construcción absoluta (i.e., es independiente de la oración principal). Así, siempre que la construcción de gerundio presente un predicado atélico obtendremos una interpretación simultánea, mientras que en los casos en los que la construcción presente un predicado télico obtendremos una interpretación de anterioridad.
Considerações semântico-pragmáticas sobre o item ‘já’
Authors: Gritti Letícia Lemos , Roehrig Teixeira Lovania , Aiolfi Gabriela Paulina Aparecida
Published: October 2024

Neste artigo discutimos características semânticas e aspectos pragmáticos do item lexical ‘já’ e, assim, procuramos entender o(s) seu(s) significado(s). Nosso objetivo é explorar alguns dos aspectos linguísticos de ‘já’, pois esse item é pouco discutido nas gramáticas tradicionais. As bases teóricas utilizadas são Gritti (2013), Lopes (2003) e Morais (2004), que abordam aspectos da semântica do item, e algumas considerações gerais de gramáticas descritivas (PERINI, 2008; NEVES, 2011). A partir da revisão bibliográfica, verificamos que ‘já’ pode ter valor temporal (localizando eventos na linha do tempo), aspectual (modificando o aspecto do evento) e conjuntivo (ligando orações) e concluímos que o item apresenta aspectos pragmáticos relevantes que o caracterizam e que não foram analisados na literatura consultada, tais como leituras de contraexpectativa e de promessa. A presença dessas leituras e a natureza das inferências que as geram foram investigadas neste artigo em sentenças no modo indicativo (presente, passado e futuro) e imperativo, estando as leituras de contraexpectativa e de promessa ausentes do último. Após testes de acarretamento e pressuposição e de cancelamento de implicatura, as leituras de contraexpectativa e de promessa revelaram-se implicaturas conversacionais, sendo, assim, inferências de natureza pragmática.
Travelling in time with natural language: Some cross-linguistic considerations
Authors: Muller Ana , Donazzan Marta
Published: October 2024

This paper investigates the grammatical strategies deployed by natural languages in order to express temporal reference. We show that temporal reference is obtained by combining a finite set of pieces of meaning which are constrained by the metaphysics of natural language (BACH 1986) and which languages distribute differently across functional categories. The paper discusses more specifically temporal adverbial clauses that express the meanings of anteriority and posteriority with respect to some reference time. We consider a relevant set of languages that make use of different strategies in order to generate these meanings, and conclude that the tools that languages may deploy are of a limited number, and include tense, aspect and temporal connectives.
Presentation of the volume 64 – New developments in semantics and pragmatics
Authors: Mendes Luciana Sanchez , Laca Brenda
Published: October 2024

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ACOLHIMENTO ÀS GESTANTES NO ACOMPANHAMENTO PRÉ-NATAL NA ATENÇÃO PRIMÁRIA À SAÚDE
Authors: Moura e Silva Chirley Araújo , Rodrigues Giselly Oliveira Fonseca , Barbosa Kalliny Mirella Gonçalves
Published: October 2024

Prenatal care is monitoring the progress of pregnancy and aims to embrace, care for and prepare women for motherhood. In view of this, this moment needs to be safe and healthy; therefore, effective, adequate, embracing and holistic maternal care is essential. This work sought to understand the perception of pregnant women regarding the embracement obtained during prenatal care in Primary Health Care. This is a study with an exploratory qualitative design, developed in a health unit located in the municipality of Juazeiro, Bahia. Semi-structured interviews were carried out with random recruitment during the doctors' appointments and the content collected was analyzed and organized into categories according to the Collective Subject Discourse technique. Thus, it was clear that good practices in the professionals' work improve processes and provide quality, humanized, safe and effective assistance to pregnant women.
Attention is all you need: An analysis of the valuation of artificial intelligence tokens
Authors: Akpan Mfon
Published: October 2024

This study discusses the parameters that define the value of artificial intelligence (AI) tokens based on user interaction, their pricing mechanism, and their correlation with the predicted value thus evaluating AI token valuation based on user engagement, pricing, and website visits. This study tests hypotheses that examine the factors that influence the value of AI tokens. Using data from ten AI tokens, the study employs correlation and regression analyses to examine these relationships. The results show that monthly active users (MAU) and website visits significantly predict valuation, while pricing shows a marginal effect. This research provides insights for stakeholders in understanding economic factors affecting AI token values, emphasizing user engagement and pricing strategies.
The Mediating Effect of Teacher’s Play Support Competency on the Relationship between Teachers' Play Beliefs and Children's Playfulness
Authors:   The Korea Associantion For Early Childhood Education Administration, Kim Eun-Jin , Choi Eun-A
Published: October 2024

The purpose of this study was to examine the mediating effect of early childhood teacher’s play support competency on the relationship between teachers' play beliefs and children's playfulness. To this end, a questionnaire was administered to 246 classroom teachers of 3-5 year olds in daycare centers and kindergartens in B, U, and K cities. To analyze the final 246 collected data, descriptive statistics, one-way analysis of variance, pearson correlation coefficient analysis, and mediation effect analysis were conducted using SPSS 25.0. The results of the analysis are as follows. First, there were differences in their play support competency depending on the type of organization they work for and their final education level. Teachers' play support competency was significantly higher in workplace daycare centers than in public kindergartens, and teachers who graduated from graduate school were significantly higher than teachers with less than a college degree. Second, early childhood teachers' play beliefs, play support competency, and children's playfulness were positively related. Third, teachers' play support competency were found to have a partial mediating effect on the relationship between teachers' play beliefs and children's playfulness. Based on these results, the relationship between teachers' play beliefs, play support competency and children's playfulness was discussed. And implications for preservice and in-service teacher education were presented.
Kazakhstan’s Resource Economy: Diversification Through Global Value Chains
Authors:   Asian Development Bank
Published: October 2024

В данном отчете приведен анализ того, как Казахстан может диверсифицировать свою ресурсозависимую экономику, стимулировать инновации и усилить глобальную рыночную интеграцию для поддержания устойчивого долгосрочного роста и ускорения перехода к экономике с высоким уровнем дохода.
Eighteen-month hybrid closed-loop use in very young children with type 1 diabetes: a single-arm multicenter trial
Authors: Ware Julia , M Allen Janet , K Boughton Charlotte , E Wilinska Malgorzata , Hartnell Sara , Thankamony Ajay , de Beaufort Carine , M Campbell Fiona , Fröhlich-Reiterer Elke , Fritsch Maria , E Hofer Sabine , M Kapellen Thomas , Rami-Merhar Birgit , Tauschmann Martin , Hovorka Roman
Published: October 2024

Objective We aimed to evaluate the longer-term safety and efficacy of hybrid closed‑loop therapy in very young children with type 1 diabetes (T1D). Research Design and Methods Following a 16-week multi-national, randomized crossover trial comparing hybrid closed-loop (CL) with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared to the primary phase SAP period and primary phase CL period. Results After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean±SD age 6.6±1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9‑10.0mmol/L was 8.4 percentage points (95% CI 6.7 to 10.1; p<0.001) higher, while HbA1c was 0.4% ([5.0mmol/mol], 95% CI 0.3 to 0.6 [3.7 to 6.2]; p<0.001) lower during the CL extension phase compared to primary phase SAP period. At 18 months mean HbA1c was 6.7±0.5% and TIR 70±7%, compared to 6.7±0.5% and 71±6% in the primary phase CL period. Time in hypoglycemia (<3.9mmol/L) was similar between CL extension phase and both primary phase SAP and CL periods (p=0.31 and p=0.70 respectively). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. Conclusions Use of the Cambridge hybrid closed-loop system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D.
Evaluating the causal effect of circulating proteome on the glycemic traits: Evidence from Mendelian randomization
Authors: Xing Xing , Xu Siqi , Wang Yining , Shen Ziyuan , Wen Simin , Zhang Yan , Ruan Guangfeng , Cai Guoqi
Published: October 2024

Abstract

Exploring the mechanisms underlying abnormal glycemic traits is important for deciphering type 2 diabetes and characterizing novel drug targets. This study aimed to decipher the causal associations of circulating proteins with fasting glucose (FG), 2-h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) using large-scale proteome-wide Mendelian randomization (MR) analyses. Genetic data on plasma proteomes were obtained from ten proteomic genome-wide association studies (GWAS). Both cis- and cis+trans-protein quantitative trait loci (pQTLs) MR analyses were conducted. Bayesian colocalization, Steiger filtering analysis, assessment of protein-altering variants, and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings. Protein-protein interaction, pathway enrichment analysis, and evaluation of drug targets were performed. Thirty-three proteins were identified with causal effects on FG, FI, or HbA1c but not 2hGlu in the cis-pQTLs analysis, and 93 proteins had causal effects on glycemic traits in the cis+trans-pQTLs analysis. Most proteins were either considered druggable or drug targets. In conclusion, many novel circulating protein biomarkers were identified to be causally associated with glycemic traits. These biomarkers enhance the understanding of molecular etiology and provide insights into the screening, monitoring, and treatment of diabetes.

Article Highlights

l Why did we undertake this study?

l Proteins are the key functional units of biology and disease and may play a role in abnormal glycemic traits.

l What is the specific question(s) we wanted to answer?

l To identify circulating proteins associated with glycemic traits using Mendelian randomization (MR)-based analytical framework.

l What did we find?

l We found multiple proteins that showed causal effects on abnormal glucose metabolism.

l What are the implications of our findings?

l These proteins may enhance the understanding of molecular etiology and provide insights into the screening, monitoring, and treatment of diabetes.
Multi-Omics Mendelian Randomization Study Investigating the Impact of PCSK9 and HMGCR Inhibition on Type 2 Diabetes Across Five Populations
Authors: B. Rosoff Daniel , Wagner Josephin , Jung Jeesun , Pacher Pal , Christodoulides Constantinos , Davey Smith George , Ray David , W. Lohoff Falk
Published: October 2024

ABSTRACT

The prevalence of type 2 diabetes (T2D) varies among populations of different race/ethnicity. The influence of genetically-proxied lipoprotein cholesterol (LDL-C) lowering through proprotein convertase subtilisin/kexin 9 (PCSK9) and HMG-CoA Reductase (HMGCR) on T2D in non-European populations is not well established.A drug-target Mendelian randomization (MR) approach was used to assess the effects of PCSK9 and HMGCR inhibition on T2D risk and glycemic traits in five populations: East Asian (EAS), South Asian (SAS), Hispanic (HISP), African (AFR), and European (EUR). Our study did not find relationships between genetically-proxied PCSK9 inhibition and T2D risk in EAS (odds ratio [OR]=1.02, [0.95-1.10]), SAS (OR=1.05, [0.97-1.14]), HISP (OR=1.03, [0.94-1.12]), or EUR (OR=1.04, [0.98-1.11]). However, in AFR, primary analyses suggested an increased risk of T2D due to PCSK9 inhibition (OR=1.53, [1.058-2.22], P-value=0.024), although this was not supported in sensitivity analyses. Genetically-proxied HMGCR inhibition was associated with an increased risk of T2D in SAS (OR=1.44, [1.30-1.61], P-value=9.8×10-12), EAS (OR=1.36, [1.22-1.51], P-value=4.2×10-10), and EUR (OR=1.52, [1.21-1.90], P-value=3.3×10-4). These results were consistent across various sensitivity analyses, including colocalization, indicating a robust finding. The findings indicate a neutral impact of long-term PCSK9 inhibition on T2D and glycemic markers in most non-European populations, with a potential increased risk in AFR cohorts. By contrast, HMGCR inhibition increased the risk of T2D in South Asian, East Asian, and European cohorts, underscoring the need to consider diversity in genetic research on metabolic diseases.

ARTICLE HIGHLIGHTS

o This study investigates the impact of lipid-lowering therapies, specifically PCSK9 and HMGCR inhibition, on type 2 diabetes (T2D) risk across diverse populations using Mendelian randomization (MR) analyses.

o We found no adverse effect of PCSK9 inhibition on T2D risk in EAS, SAS, HISP, or EUR populations, though weak evidence of increased risk was seen in AFR, which was not robust in sensitivity analyses.

o HMGCR inhibition was associated with a slight increase in T2D risk, consistent with previous findings, but the cardiovascular benefits of statin therapy likely outweigh this risk.
The models for the study of biological properties of human hematopoietic stem cells
Authors: Ustyugov A. Yu , Rumyantsev S. A
Published: October 2024

The article describes different experimental in vivo models applied to achieve knowledge of hemopoiesis and stem cell source-dependent mechanisms of engraftment. Although all the models have relative advantages and drawbacks, they all have one common feature - the cord blood engraftment kinetics are better, than those of bone marrow stem cells, while those are superior to peripheral blood mobilized stem cells. In spite of all the progress achieved by prolonged research, the cause of relatively low level of the human cells generated in these models is still unclear. The solution to this problem may be found with the aid of gene engineering achievements.
Possibility of application primary cell culture of kidney newborn rabbits in vaccines production
Authors: Glagoleva I. S , Plotnikova E. M
Published: October 2024

Possibility of application of primary cell cultures in production of vaccines for domestic animals has been presented in this paper. Also the comparative description of application of organ cultures, cell lines and strains in virology has been provided. We have analyzed the different methods of receiving primary cultures. Also we presented our own data of primary cell cultures sensitivity to various virus agents of domestic animals on the example of the cell culture of kidney newborn rabbits.
Proliferative and differentiation potential of adipose tissue-derived mesenchymal stromal cells in the presence of platelet lysate
Authors: Rogulska O. Yu , Revenko O. Б , Petrenko Yu A. , Petrenko A. Yu
Published: October 2024

Clinical application of mesenchymal stromal cells requires the development of serum-free culture medium for optimal cell growth and differentiation. Platelet lysate as an alternative for xenogeneic fetal serum is able to promote expansion of human adipose tissue-derived mesenchymal stromal cells. Platelet lysate stimulates the proliferative activity of cells and increases the efficiency of colony formation. When cultured mesenchymal stromal cells in the presence of platelet lysate we identified colonies of the same types as in the presence of fetal bovine serum, but their ratio changes in favor of dense and mixed colonies compared with diffuse colonies. Size and density of the cell colonies formed in the presence of platelet lysate are higher than in those in serum. After expansion in medium with 10% platelet lysate mesenchymal stromal cells retain the ability to differentiate into osteogenic and adipogenic directions while efficiency of osteogenic differentiation of these cells is better than of cells previously expanded in the presence of serum. The results of current study show that platelet lysate is a promising natural substitute for xenogeneic serum in optimizing culture technology of human mesenchymal stromal cells for regenerative medicine and tissue engineering.
Decellularized human umbilical arteries retain their mechanical properties
Authors: Nasredinov A. S , Lavreshin A. V , Lebedeva E. A , Anisimov S. V , Vavilov V. N , Kurapeev D. I
Published: October 2024

Tissue engineered vascular grafts can fulfill a clinical need in biological prostheses in reconstructive cardiovascular surgery. Decellularized arteries do not cause immune response, are biocompatible, could be reseeded with recipient cells und thus are attractive scaffolds for vascular tissue engineering. Earlier we developed a decullarization method for human umbilical arteries and proved its effectiveness morphologically. The purpose of this study was to evaluate mechanical properties of the decellurized human umbilical arteries, also after long-term storage. 3 groups of vessels were investigated: I group - native arteries, II group - decellularized arteries, III group - decellularized arteries, stored in phosphate buffered saline for 10 months. Samples were stretched until rupture on the Instron universal testing machine; herewith strain and stress were recorded. The same way the suture retention strength was estimated. Also burst-pressure, that characterized the total strength of the samples, was investigated. Intergroup differences in maximum strain both longitudinal and transverse directions, suture retention strength and burst pressure were not significant. Decellularized human umbilical arteries retain their mechanical properties, and that indirectly confirms extracellular matrix preservation. Thus they are attractive source for small diameter tissue engineered vascular grafts.
Histotechnical solutions for quality improvement of nucleic acid specimens extracted from paraffin blocks
Authors: Vaganova A. N
Published: October 2024

With the growing body of information about molecular nature of a set of diseases, the question of molecular biology techniques acceptability for histological material study came up. Currently available pathology archives could provide vast quantity of material for retrospective studies, however, the most frequently used fixative formalin dramatically damages nucleic acids in the tissue. A similar problem arises with the material that come into the pathology department and undergoing conventional histological processing in nowadays. In recent years with the entry into the practice of diagnostic methods based on molecular biology methods it has become especially important to obtain high-quality samples of nucleic acids. Research devoted to development of new approaches of histological material handling from one side and solutions for nucleic acids extraction from tissue after standard histological treatment on the other side revealed a number of ways to overcome the problem of poor quality of nucleic acids isolated from the paraffin block. The aim of this review is to highlight the modifications histological processing techniques that allow prepare nucleic acids samples of higher quality.
Influence of liver perisinusoidal cell transplantation on liver regeneration after damage induced by CCL4 and 2-acetylaminofluorene
Authors: Burganova G. R , Titova A. A , Sharipova E. I , Pevnev G. O , Mavlikeev M. O , Gazizov I. M , Galyavieva A. R , Shafigullina A. K , Kaligin M. S , Titova M. A , Gumerova A. A , Kiassov A. P
Published: October 2024

Research in the past decade allows us to consider liver perisinusoidal cells as a possible regional stem cells of the liver. Despite of this, there is no work dedicated to study their influence to liver regeneration. The aim of this work was to study liver regeneration after liver perisinusoidal cell transplantation in rats with CCL4 and combination of CCL4 and 2-acetylaminofluorene damage. Our results showed that in both models of toxic damage transplanted perisinusoidal cells are found in the recipient's liver and exhibit the properties of stem cells by differentiation into hepatocytes. Transdifferentiation of injected cells into myofibroblasts was not detected which indicates the absence of liver fibrosis risk after use of this cell type for cell therapy.
Binase induces pro-inflammatory immune response of macrophages
Authors: Lozhkin A. P , Zelenikhin P. V , Makeeva A. V , Sokolova E. A , Ilinskaya O. N
Published: October 2024

Biopharmaceutical agents, especially proteins, may possess a broad spectrum of immunological effects. Cytotoxic ribonucleases, such as binase - RNase of Bacillus pumilus, have a significant potential as anticancer therapeutical agents. However without comprehensive analysis of immune system reactions on the proteins, the practical utility of them is complicated. Using the flow cytometry we estimated qualitative and quantitative changes in IL-6, IL-10, МСР-1 and TNF-acytokines synthesis by peripheral macrophages of mice under the influence of binase and RNAse A. We established that binase in concentration 100 and 300 jg/ml, in contrast to RNase A, is able to activate pro-inflammatory response of macrophages, inducing increase of IL-6, МСР-1 andTNF-a cytokines level in cultural media. Treatment with RNases does not enhance the antiinflammatory cytokime IL-10 synthesis. Obtained data lead as to the assumption, that binase capability to activate pro-inflammatory response of macrophages will intensify its antitumor effects in vivo.
Oral mucosais a new source for myoblast derivation
Authors: Zorin V. L , Eremin I. I , Rybko V. A , Zorina A. I , Kotenko K. V , Pulin A. A , Kopnin P. B
Published: October 2024

Leading laboratories in the world intensively research tissue-specific stem cells. The main goal of such work is development of improved technique of tissue regeneration stimulation. Optimization of conditions of differentiation induction, and search for new sources of cells are actual problems in this field of science. Human gingival mucosa is one of promising sources of cells. Gingival mucosa-derived multipotent mesenchymal stromal cells (gm MMSC) have a number of features, notably the high proliferative activity and ability to multilineage differentiation. However, their myogenic differentiation has not been proofed yet. The study was conducted on 10 gm MMSC cultures obtained from gingival mucosa biopsy samples of 10 healthy volunteers. Possibility of gm MMSC obtainment with high proliferative potential and ability of cells to efficiently differentiate not only into orthodox (adipogenic, osteogenic, chondrogenic) directions but also in myogenic direction during both early and late passages was demonstrated for the first time in our work. Our results of gm MMSC investigation and characteristics of the cell'ssource, confirm advantages of gm MMSC use in regenerative medicine, in particular for the treatment of the muscle tissue diseases of different etiology.
Phenotypic modifications and quantitative analysis of glial cells in the area of spinal cord injury at the cell-mediated and direct gene delivery gdnf
Authors: Mukhamedshina Y. O , Shaymardanova G. F , Mukhitov A. R , Garanina E. E , Rizvanov A. A , Chelyshev Yu. A
Published: October 2024

On the model of rat spinal cord dosed contusion at T8 level studied the effect of delivery into the area of damage of the cell-mediated and direct gene delivery GDNF on maintaining a population of glial cells. Delivery into the area of damage adenoviral vector with gene GDNF (AdV-gdnf) using human umbilical cord blood mononuclear cells has a greater influence the amount of Ch47+-cells in the ventral horn (VH). Direct delivery of AdV-gdnf influences the amount of Ch47+-cells in dorsal roots entry zone (DREZ). Cell-mediated gene delivery GDNF causes the most pronounced changes in the expression of marker proteins astrocyte GFAP, S100B, and AQP4 in the ventral funiculus (VF) of white matter. Cell-mediated and direct delivery of gene GDNF support population GFAP+/S100B+-cells. The results indicate that the direct and cell-mediated gene delivery GDNF into spinal cord injury have different effects on the populations of glial cells in specific areas of spinal cord, that is important for the optimal method of delivery of therapeutic genes to stimulate posttraumatic neuroregeneration.
The combination of intestinal chelators for correction of environmentally caused by trace element imbalance in children at the cellular level
Authors: Tunakova J. A , Fayzullin R. I , Valiev V. S
Published: October 2024

Normally, the human body maintains a certain balance of micronutrients. The danger of a constant inflow of toxic elements from the environment caused by the inability to selfdestruction and elimination from the body, so the search for an optimal balance correction of metals is carried out. By AAS definition of the nine most common toxic and essential trace elements in hair of children in all 11 children's clinics service areas was held: Pb, Cu, Zn, Cr, Sr, Mn, Ni, Fe, Cd. Six different types of biopolymer ehnterosorbents: pectin, alginates, chitosan, microcrystalline cellulose and chitin were studied in the proposed model. A method of produce and combination of biopolymer and mineral enterosorbents with qualitatively new properties and lower cost compared to monosorbents was developed. 11 most common toxic and essential trace elements in hair of children were analyzed. The most variable and requiring of geographically differentiated correction elements in areas of research were determined. The most effective biopolymer enterosorbents and their combinations with mineral enterosorbents were discovered. Experimentally a method of producing composite enterosorbents based colloids was created. The highest sorption capacity related to of Zn, Cd, Fe and Cu requiring geographically differentiated correction was noted in combination of octahedral smectite and chitosan tests.
Experience of preserved corneal transplantation for penetrating keratoplasty
Authors: Taldaev R. E , Andreeva D. I , Kiassov A. P
Published: October 2024

Corneal diseases are one of the leading causes of blindness and poor vision. Keratoplasty is the only effective method of treatment in case of corneal lesion or perforation. Since the use of the native cornea is restricted by the lifespan of the material and its limited availability, it is reasonable to use the preserved corneal transplants, especially in case of emergency. The analysis of 26 penetrating keratoplasties is adduced. One group of patients (22 eyes) were performed elective surgery, and the second group (4 eyes) - urgent intervention. Patients were follow-upped for 24 months. All patients were examined by standard methods, additionally; the amount of endothelial cell was counted. Transparent engraftment was achieved on 18 eyes (81%) in the first group and three eyes (75%) in the second group. Endothelial cell density was 1500±200/mm2. Visual acuity after surgery varies depending on the disease that caused keratoplasty, postoperative course, and the condition of posterior segment of the eye. Preserved cornea is a safe against blood transmitted infections, makes a penetrating keratoplasty possible in various diseases of the cornea, including the need for emergency surgery, and allows achieving a transparent and translucent engraftment in most cases.
Pharmacogenetic and bioengineering approaches to the treatment of glial tumors of the brain
Authors: Bryukhovetskiy I. S , Bryukhovetskiy AБ. S , Khotimchenko Y. S
Published: October 2024

The article analyzes the existing ideas about the specific mechanisms of therapeutic resistance of glial tumors of the brain, systematized the main trends in modern chemotherapy glial tumors, an attempt to justify the new bioengineering approaches to the creation of personalized cell preparations for therapy of glial tumors based on molecular - biological characteristics of tumor stem cells. It is shown that the main tool of the therapeutic effects can be own stem cells of cancer patients and tumor stem cell proteome can be considered as the primary target cell therapy.
The role of cytokine system RANKL/RANK/OPG in the regulation of bone metabolism
Authors: Aganov D. S , Tyrenko V. V , Tsygan E. N , Toporkov M. M , Bologov S. G
Published: October 2024

The review describes the modern data concerning the cellular and molecular mechanisms of mineral metabolism disturbance in bone tissue. Cytokine system consisting of receptor activator of nuclear factor к-b, its ligand and osteoprotegerin (RANKL/RANK/OPG) has a key role in understanding of bone remodeling regulation. We discuss a significance of the cytokine system in osteoblasto- and osteoclastogenesis. Molecular processes of histogenesis and bone resorption have been analyzed.
Delivery of nerve growth factor (NGF) gene via recombinant plasmid vector induces angiogenesis in murine ischemic hind limb
Authors: Boldyreva MA. A , Makarevich P. I , Rafieva L. M , Beloglazova I. B , Dergilev K. V , Kostrov S. V , Parfyonova Ye. V
Published: October 2024

The development of therapeutic angiogenesis that can stimulate the formation of mature vessels is a valuable prospect for treatment of ischemic disease, and the combination of well-known angiogenic factors with other growth factors is now beginning to show promise in therapy. In our efforts to identify possible targets for therapeutic intervention using combinations of growth factors, nerve growth factor (NGF) seems to be a possible candidate. In this study we analyzed the possibility to stimulate angiogenesis via local delivery of a plasmid encoding human nerve growth factor (hNGF). We used a murine hind-limb ischemia model to assess plasmid angiogenic potential in vivo. Plasmid DNA was diluted in saline and injected into ischemic m. tibialis anterior. Blood flow restoration was analyzed by laser Doppler imaging every 7 days after surgery, and throughout the experiment we assessed total hind-limb necrosis. After animals were sacrificed, muscle samples were frozen for histological analysis. Tissue sections were stained with antibodies against endothelium marker CD31 to assess vascular density. Blood perfusion by day 7 was higher in the NGF-treated group compared to control (p = 0.01), and by day 14 animals in the NGF-treated group had perfusion 2.8 fold higher than control animals (NGF 44.62±7.68; control 16.74±5.85; р = 0.005). Vascular density in tissue samples by day 14 in NGF-treated animals was about 2-fold higher than in the control group (р
Recovery of ulnar nerve defect by autonerve grafting and autotransplantation of stromal vascular fraction of adipose tissue
Authors: Masgutov R. F , Gallyamov A. R , Shulman A. A , Bogov (jr) A. A , Khannanova I. G , Mullin R. I , Salafutdinov I. I , Topyrkin V. G , Rizvanov A. A , Bogov A. A
Published: October 2024

This article describes a clinical case of treating the patient with injury of ulnar nerve using a “gold standard” of microsurgery, the autonerve grafting, and transplantation of autologous cells of stromal vascular fraction (SVF) of adipose tissue. Nerve defect in 5 cm was replaced by three autonerve grafts of the sural nerve, and then autologous cells of SVF in the fibrin glue were transplanted. 1 year after operation, the patient has resumed the function of bringing the fingers, there have not been any neurogenic strain, muscle atrophy of the hand, as well as restoration of sensitivity in the autonomous zone of innervation of the ulnar nerve has been observed.
Characteristics of neoosteogenesis in the model of critical defect of rats' parietal bone using traditional and three-dimensional morphometry
Authors: Vasilyev A. V , Volkov A. V , Bolshakova G. B , Goldstein D. V
Published: October 2024

We modified the techniques of 3D-morphometry using histological sections based on computer-generated ЗЮ reconstruction and mathematical modeling. We compared the results of measurements obtained with the use of above methods and those taken with traditional methods based on the analysis of X-ray pictures. It was shown that the methods of 3D-morphometry we developed provided more precise evaluation of the size of newly formed bone tissue. Basis for technical recommendations to perform the 3D-morphometry at every stage, from surgery to morphological analysis, were proposed.
Peripheric disfunction as one of the mechanisms of pathogenesis of neurodegenerative disesases
Authors: Mukhamedyarov M. A , Martinov A. V , Petukhova E. O , Grigoryev P. N , Eshpay R. A , Rizvanov A. A , Zefirov A. L
Published: October 2024

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, etc. affect 20-25% of elderly population, making this one of the main problems of modern society. Data accumulating during recent years certify that neurodegenerative diseases are related to disorders of not only structures on central nervous system, but of peripheral tissues and organs as well. In particular, dysfunction of peripheral excitable structures of neuromuscular and cardiovascular systems was established. These disturbances can play significant role in pathogenesis of neurodegenerative diseases, contributing to development of pathological processes underlying disability and death of patients (skeletal muscle atrophy and paralysis, myocardium infarction, etc.). Pathology of neuromuscular and cardiovascular systems in neurodegenerative diseases is not just “reflection” of degenerative changes in central nervous system, but particular, virtually unexplored aspect of pathogenesis of these maladies Peripheral dysfunctions in neurodegenerative diseases can be primary or amplifying degenerative processes in central nervous system, which further increases their importance in the development of the disease . In this paper, we conduct a detailed review of available literature and our own data on the dysfunction of the peripheral excitable structures in neurodegenerative diseases, and the role of these disorders in pathogenesis and clinical course of these pathologies
Prospects of EPR spectroscopy to the intensity of free radical processes evaluation in tissue-engineering esophagus and diaphragm
Authors: Gubareva E. A , Basov A. A , Kuevda E. V , Sotnichenko A. S , Dzhimak S. S , Bolotin S. N , Gilevich I. V , Danilenko K. A , Gumenyuk I. S , Markushin V. A , Porhanov V. A , Macchiarini P.
Published: October 2024

Tissue engineering can become an alternative option of treatment which is focused on restoration, replacement and regeneration of cells, tissues and failed organs. One of the tasks of regenerative medicine is creation of biological or artificial scaffolds reproducing structure of native tissue and possessing the required physical, chemical and mechanical properties for ensuring cell adhesion and formation of three-dimensional tissue as a result of recellularization with autologous cells. Biological scaffolds must be decellularized to become nonimmunogenic; however this process has to be aimed at the maximum preservation of biochemical composition, morphological structure, and maintenance of the biomechanical properties of the obtained extracellular matrix similar to the properties of native tissue One of the main issues is development of criteria of quality of the obtained scaffolds. In this work the spectroscopy EPR (electron paramagnetic resonance) method is used as one of promising biophysical methods of evaluation of decellularization EPR-spectroscopy applicability is also shown for evaluation of preservation of native organs at a cryopreservation which might already be the first stage of decellularization that is indirectly confirmed by the conducted researches
Expression of pluripotency transcription factors in human third molar tooth germ derived multipotent mesenchymal stromal cells transfected by plasmid pBud-Sox2-Oct4
Authors: Solovyeva V. V , Blatt N. L , Guseva D. S , Yalvac M. E , Sahin F. , Islamov R. R , Rizvanov A. A
Published: October 2024

In this study, the double expression cassette plasmid, based on pBudCE4 1 vector encoding transcription factors S0X2 and 0CT4 was constructed using standard gene engineering techniques. Expression of recombinant genes was confirmed by immunoblotting. It is shown that genetic modification of multipotent mesenchymal stromal cells (MMSC), isolated from human third molar tooth germs, with resulting recombinant plasmid increases the level of expression both, transcription factors S0X2 and OCT4 in the treated cells, and also transcription factor NAN0G. Analysis of histological sections of subcutaneous Matrigel implants, containing fluorescently labeled MMSC, showed that genetic modification had no effect on cell viability
Use of stromal vascular fraction cells from adipose tissue to replace segmental defect of dog's alveolar crest: experimental case
Authors: Khairutdinova A. R , Khafizova F. A , Mirgazizov M. Z , Khafizov I. R , Zakirova E. Y , Sergeev M. A , Salafutdinov I. I , Masgutova G. A , Masgutov R. F , Rizvanov A. A , Bagmanov M. A , Mirgazizov R. M , Khafizov R. G
Published: October 2024

The paper presents a case of using autologous stromal-vascular fraction of adipose tissue to increase bone volume in the areas of dental implantation. As the matrix for cells we used nikelid-porous titanium granules which fit into the defect area alveolar with giving required volume. Throughout the experiment conducted observation of animals, accompanied by histological studies According to the results of histological studies and observations it can be concluded that the application of the proposed method of bone plastic is advisable and highly effective in the practice of medicine.
Efficiency of autofibroblasts in surgical treatment of parodontitis
Authors: Starostina I. G , Solovyeva V. V , Yuryeva K. S , Shevchenko K. G , Fedotov V. P , Rizvanov A. A , Deev R. V , Isaev A. A
Published: October 2024

Dysferlinopathies is a group of autosomal-recessive inherited neuromuscular diseases, which are characterized by defect in mRNA expression or in functionioning of dysferlin protein, appearing in about 1/200 000 births. Dysferlin is encoded by DYSF gene (Dystrophy-associated fer-1-like). It's disruption can cause various types of primary dysferlinopathies, which include Miyoshi myopathy (MM), Limb-girdle Muscular Dystrophy type 2B (LGMD2B) and distal myopathy with anterior tibial onset. Also, dysferlin deficiency can be associated with other diseases, such as caveolin- and calpainopathies. Here we discuss dysferlin protein structure and function, it's clinical phenotypes, known animal models and developing treatment strategies for dysferlinopathies.
Possible directions of human cord blood mononuclear cells differentiation in the regenerating rat liver
Authors: Andreeva D. I , Gazizov I. M , Ylmaz T. S , Kaligin M. S , Gumerova A. A , Kiyasov A. P
Published: October 2024

It is known that human cord blood hematopoietic stem cells (HSC) are able to differentiate into hepatocytes. This ability can be widely used in treatment of various liver diseases. However, there are some genetic diseases of liver, when the application of autologous stem cells is not possible. So it could be very helpful to develop methods of genetic modification of stem/progenitor cells. However, it should be proved that genetic modification does not change the properties of HSC. We performed partial hepatectomy for the white mongrel male rats and injected human umbilical cord blood mononuclear cells transfected by gene of green fluorescent protein (GFP) into the spleen. Paraffin sections of the liver were stained with antibodies to stem cell factor receptor, human leukocyte antigen, a-smooth muscle actin, enhanced GFP, cytokeratin 19, hepatocyte specific antigen, human a-fetoprotein. Also we used a double-immunohistochemical staining to detect expression of stem cell factor receptor and desmin, enhanced GFP and cytokeratin 19. Our study showed that human cord blood mononuclear cells transfected by gfp transplanted into the spleen of rats after partial hepatectomy migrated to the liver and acquired the phenotype of hepatocytes, cholangiocytes and sinusoidal cells. At the same time the differentiation of such transplanted cells into myofibroblasts, as it was previously shown, does not occur. Hepatoblasts and hepatocytes found in the liver of rats after transplantation of genetically modified and native cells express human hepatocyte specific antigen and a-fetoprotein that means they are functionally active.
Multipotent stromal cells in the treatment of acute liver failure after extended hepatectomy in the experiment
Authors: Rudakov V. S , Voskanyan S. E , Eremin I. I , Onnitsev I. E , Deev R. V , Naydenov E. V , Eremin P. S , Zhgutov Y.A.
Published: October 2024

Resection of the liver is the main method of treatment in primary and metastatic liver tumors. Frequent complication after extended hepatectomy is acute liver failure, which occurs in 33.83% of cases and may lead to death. The aim of this study is to determine the therapeutic potential of multipotent mesenchymal stromal cells in the treatment of acute liver failure after extended hepatectomy in animal models (rats). The liver mass (before and after 70% hepatectomy), synthetic function of the liver, the level of liver enzymes were measured. The results showed that transplantation of 2.5 mil. of multipotent mesenchymal stromal cells of bone marrow into the inferior vena cava improves liver function and decrease the level of liver enzymes. We observed better recovery of liver mass, and liver functional test (total protein, albumin, alkaline phosphatase, INR, APTT, direct bilirubin) in the experimental group. Thus, multipotent mesenchymal stromal cells have therapeutic effect in treatment of acute liver failure after extended hepatectomy in the experiment. However, more research is needed to understand the mechanisms of therapeutic action of these cells after extended hepatectomy.
Long noncoding RNA expression pattern in the X inactivation center of rodents
Authors: Elisaphenko E. A , Shevchenko A. I , Zakian S. M
Published: October 2024

Transcriptome analysis of several cell lines with different differentiation degree has been carried out in three rodent species - voles, rats, and mice. As a result, expression profiles of X-inactivation center genes have been generated. In mice, new data on how expression of key genes of X-inactivation center, Xist and Tsix, changes during ontogenesis have been obtained. New types of transcripts have been revealed. In voles, Xist expression was observed in all 8 cell lines examined. Interestingly, main vole Xist transcript had 7 exons as those of rats and mice. In addition, Xist antisense transcript, Tsix, was expressed in 4 vole cell lines and was presented by both spliced and unspliced variants. Expression between the Enox (Jpx) and Xist genes has been revealed in three vole cell lines. Additional variants of Tsix transcripts were observed when studied expression profiles of several rat cell lines. The variants were not present in mice and voles. Compared to mice and voles, Tsix expression level in rats was several times higher than that of Xist.