Ordinary and Activated Bone Grafts: Applied Classification and the Main Features

© 2015 R. V. Deev et al. Bone grafts are medical devices that are in high demand in clinical practice for substitution of bone defects and recovery of atrophic bone regions. Based on the analysis of the modern groups of bone grafts, the particularities of their composition, the mechanisms of their biological effects, and their therapeutic indications, applicable classification was proposed that separates the bone substitutes into "ordinary" and "activated." The main differential criterion is the presence of biologically active components in the material that are standardized by qualitative and quantitative parameters: growth factors, cells, or gene constructions encoding growth factors. The pronounced osteoinductive and (or) osteogenic properties of activated osteoplastic materials allow drawing upon their efficacy in the substitution of large bone defects

Gene- and cell-based therapy of muscle system hereditary disorders: State-of-art

Genetic disorders primarily affecting skeletal muscles can be caused by dysfunction of more than 30 genes. To date there is no effective etiotropic and pathogenetic treatment of such disorders. Investigators focus on search for new therapeutic agents based on gene and cell technologies, small molecules as well. There are numerous preclinical and several dozens of clinical studies in the world. Unfortunately tested technologies did not lead to significant advance in treatment of patients with such disorders. At the same time resulting data allow to determine the most feasible directions of future development combining of genome correction methods with cell delivery of corrected genome to skeletal muscles. This review is intended to give general information about etiology of skeletal muscles genetic disorders, the main directions of biotechnological development and results of the clinical studies

Combined use of plasmid drug pCMV-VEGFA and autodermoplasty for stimulation of skin defects healing in the experiment

© 2018 Human Stem Cell Institute. All rights reserved. To find effective ways to stimulate chronic skin wounds healing (including deep burns, diabetic and trophic ulcers) is an actual multidisciplinary task. The aim of our study was to assess the potential of using autodermoplasty in combination with plasmid drug pCMV-VEGFA to optimize skin defects repair in the experiment. Autodermoplasty was performed on Wistar rats. The size of the skin flap was 22 cm. Immediately after surgery the animals of the test group (n=8) underwent intradermal injection in the periphery of autotransplant with 1 ml solution containing 0.3 mg of supercoiled plasmid DNA pCMV-VEGFA, rats of the control group (n=8) received 1 ml of 0.9 % NaCl. The results were analyzed in 3, 6, 9 12, 18 days using macroscopic evaluation, laser Doppler flowmetry, histological methods. Macroscopically in the test group necrosis of the transplanted skin flap was found at later periods of observation, in one case complete survival of autotransplant was observed. The results of laser Doppler flowmetry in the group with plasmid DNA did not have statistically significant differences with control. The wound defect diameter in the test group at 12 days was 5,52± 4.80 mm, in the control 12,45±0,82 mm (p=0,03); 2,53±of 2,94 mm and 4,23±3,5 mm (p=0,067) at 18 days, respectively. At 18 days, the average number of vessels under the flap in the central zone were: of 26±2,9 in the test group and 20±8 in control; it the peripheral zone 27±3,4 and of 12,1±3,9 (p=0,035), respectively; in the skin muscle 21,2±of 3,9 and 12,4±3,6 (p=0,04), respectively. Thus, the use of plasmid drug pCMV-VEGFA improved the skin healing after autodermoplasty

Towards improving early diagnosis of congenital Chagas disease in an endemic setting.

: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect &gt;50% of infected neonates and 9 month follow-up is low. : Women presenting for delivery in two urban hospitals in Santa Cruz department, Bolivia were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR) and IgM trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month, and by IgG serology at 6 and 9 months. : Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1% and 16.7%/100%, respectively. When birth and 1 month results were combined, cumulative sensitivities reached 84.2%, 73.7% and 34.2%, respectively. Low birth weight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. : The proportion of T. cruzi infected infants with clinical signs has fallen from the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit increasingly challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.<br/

Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia

Vector exposure showed a direct association with Chagas cardiomyopathy, but an inverse relationship with maternal parasitemia and congenital transmission. We hypothesize that repeated antigen exposure maintains an inflammatory response, increasing cardiomyopathy, but this upregulation improves control of parasitemia during pregnanc

Toward Improving Early Diagnosis of Congenital Chagas Disease in an Endemic Setting.

BACKGROUND: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. METHODS: Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. RESULTS: Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. CONCLUSIONS: The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Biological activity comparative evaluation of the gene-Activated bone substitutes made of octacalcium phosphate and plasmid DNA carrying VEGF and SDF genes: Part 1 - in vitro

High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-Activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor- 1α (SDF-1α). The aim of the study was to evaluate the cytotoxicity of the gene-Activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-Activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-Activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-Activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo

Effects of autologous gingiva-derived cells with myogenic potential on regeneration of skeletal muscle

In our recent studies we found for the first time the ability of human multipotent mesenchymal stromal cells (MSCs) derived from alveolar gingiva (alveolar mucosa) to differentiate into myogenic direction. The aim of the present study was to evaluate the effects of autologous gingiva-derived MSCs with myogenic potential on the regeneration of muscular tissue after mechanical damage. The study was conducted on 11 male rabbits. Biopsy of alveolar gingiva was performed at each animal before experiment for autologous MSCs obtainment. Cultures of MSCs were induced in vitro into myogenic direction. To model the damage, the medial heads of the gastrocnemius muscles were intersected on both pelvic limbs of the rabbit. Injection of autologous MSCs was performed on the seventh day after injury into the damaged muscle of one of the extremities, while equal volume of saline (control) was injected into the muscle of the contralateral limb. The animals were sacrificed on 0, 21, and 35 days after the administration of cells. MSCs transplantation led to significant reduction of the area of muscle damage. Immunohistochemical analysis revealed earlier increase in the proportion of MyoD- and myogenin-positive cells, as well as decrease in the expression of Ki-67 in damaged tissue, in experimental group compared to the control. Autologous cells did not significantly affect the composition of muscle fibers. Significant decrease in the proportion of fibrous tissue was also observed in the experimental group. The results indicate the effectiveness of autologous alveolar gingiva-derived MSCs for treatment of mechanical damage of muscle tissue. Local administration of cells accelerated reparative regeneration and prevented fibrosis

Potential causal association between gut microbiome and posttraumatic stress disorder

Funding Information: We thank the participants and working staff including the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, the FinnGen consortium, and the MiBioGen consortium. Publisher Copyright: © 2024, The Author(s).Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.publishersversionpublishe