Transformative vaccination: A pentavalent shield against COVID-19 and influenza with betulin-based adjuvant for enhanced immunity.

The development of an effective combined vaccine represents a crucial strategy for preventing outbreaks of infectious diseases and reducing the burden on healthcare resources. Developing a combined vaccine against both influenza and the coronavirus is a promising approach, but it is still in the early stages of development. This paper reports on a novel combined pentavalent candidate vaccine that has shown promising results in mice, with statistically significant differences in mean antibody titer against the coronavirus and the influenza antigens compared to placebo.

Dual Adeno-Associated Virus 9 with Codon-Optimized DYSF Gene Promotes In Vivo Muscle Regeneration and May Decrease Inflammatory Response in Limb Girdle Muscular Dystrophy Type R2.

Dysferlinopathy treatment is an active area of investigation. Gene therapy is one potential approach. We studied muscle regeneration and inflammatory response after injection of an AAV-9 with a codon-optimized DYSF gene.

Dermal Fibroblasts as the Main Target for Skin Anti-Age Correction Using a Combination of Regenerative Medicine Methods.

This article includes the data from current studies regarding the pathophysiological mechanisms of skin aging and the regenerative processes occurring in the epidermis and dermis at the molecular and cellular level, mainly, the key role of dermal fibroblasts in skin regeneration. Analyzing these data, the authors proposed the concept of skin anti-age therapy that is based on the correction of age-related skin changes by stimulating regenerative processes at the molecular and cellular level. The main target of the skin anti-age therapy is dermal fibroblasts (DFs).

In Vivo DYSF Gene Viral Delivery Provides a Histoprotective Effect in Skeletal Muscle Tissue in Dysferlin-Deficient Mice.

We studied the effects of a dual-vector DYSF gene delivery system based on adeno-associated virus serotype 9 capsids on pathological manifestations of dysferlinopathy in skeletal muscles of Bla/J mice lacking DYSF expression. The mice received intravenous injection of 3×10 genomic copies of the virus containing the dual-vector system. M.

Commercial articulated collaborative 3D bioprinter for skin wound healing.

bioprinting is one of the most clinically relevant techniques in the emerging bioprinting technology because it could be performed directly on the human body in the operating room and it does not require bioreactors for post-printing tissue maturation. However, commercial bioprinters are still not available on the market. In this study, we demonstrated the benefit of the originally developed first commercial articulated collaborative bioprinter for the treatment of full-thickness wounds in rat and porcine models.

Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial.

Unlabelled: COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies.

Correlation of the regenerative potential of dermal fibroblasts in 2D culture with the biological properties of fibroblast-derived tissue spheroids.

In situ 3D bioprinting is a new emerging therapeutic modality for treating human skin diseases. The tissue spheroids have been previously suggested as a powerful tool in rapidly expanding bioprinting technology. It has been demonstrated that the regenerative potential of human dermal fibroblasts could be quantitatively evaluated in 2D cell culture and confirmed after implantation in vivo.

SARS-CoV-2 Subunit Virus-like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study.

Public health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of "Betuvax-CoV-2", a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based spherical virus-like nanoparticles as an adjuvant ("Betuspheres"). The study aimed to demonstrate vaccine safety in mice, rats, and Chinchilla rabbits through acute, subchronic, and reproductive toxicity studies.

Molecular Mechanisms of Changes in Homeostasis of the Dermal Extracellular Matrix: Both Involutional and Mediated by Ultraviolet Radiation.

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. With age, an impairment of structures, quality characteristics, and functions of the dermal extracellular matrix (ECM) occurs in the skin, which leads to disrupted functioning of dermal fibroblasts (DFs), the main cells supporting morphofunctional organization of the skin. The DF functioning directly depends on the state of the surrounding collagen matrix (CM).

COVID-19 pandemic in Saint Petersburg, Russia: Combining population-based serological study and surveillance data.

Background: The COVID-19 pandemic in Russia has already resulted in 500,000 excess deaths, with more than 5.6 million cases registered officially by July 2021. Surveillance based on case reporting has become the core pandemic monitoring method in the country and globally.

Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging.

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced.

Design and Immunological Properties of the Novel Subunit Virus-like Vaccine against SARS-CoV-2.

The COVID-19 pandemic is ongoing, and the need for safe and effective vaccines to prevent infection and to control spread of the virus remains urgent. Here, we report the development of a SARS-CoV-2 subunit vaccine candidate (Betuvax-CoV-2) based on RBD and SD1 domains of the spike (S) protein fused to a human IgG1 Fc fragment. The antigen is adsorbed on betulin adjuvant, forming spherical particles with a size of 100-180 nm, mimicking the size of viral particles.

Seroprevalence of SARS-CoV-2 antibodies in Saint Petersburg, Russia: a population-based study.

Properly conducted serological survey can help determine infection disease true spread. This study aims to estimate the seroprevalence of SARS-CoV-2 antibodies in Saint Petersburg, Russia accounting for non-response bias. A sample of adults was recruited with random digit dialling, interviewed and invited for anti-SARS-CoV-2 antibodies.

Bringing a Gene-Activated Bone Substitute Into Clinical Practice: From Bench to Bedside.

Bone grafting and reconstruction are still challenging in clinical practice because of the limitations of bone autografts and the drawbacks of currently approved bone substitutes. We thus developed a gene-activated bone substitute based on octacalcium phosphate and naked plasmid DNA carrying the vascular endothelial growth factor gene. This advanced combined therapy medicinal product had no cytotoxic effects , slightly decreased bone marrow mesenchymal stromal cell (MSC) doubling time, and was characterized by a prolonged level of gene construct delivery in a luciferase bioimaging assay.

Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene.

A family of five male siblings (three survivors at 48, 53 and 58 years old; two deceased at 8 months old and 2.5 years old) demonstrating significant phenotypic variability ranging from intermediate to the myosclerotic like Bethlem myopathy is presented. Whole-exome sequencing (WES) identified a new homozygous missense mutation chr21:47402679 T > C in the canonical splice donor site of the second intron (c.

3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.

The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on octacalcium phosphate (OCP) and plasmid DNA encoding . The first objective of the present work involved design and fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with gene using 3D printing approach of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and compressive strength analyses were applied to investigate the chemical composition, microstructure, and mechanical properties of the experimental samples.

In Vitro Angiogenic Properties of Plasmid DNA Encoding SDF-1α and VEGF165 Genes.

The stromal-derived factor-1 alpha (SDF-1α) and vascular endothelial growth factor (VEGF) play an important role in angiogenesis and exert a significant trophic function. SDF-1α is a chemoattractant for endothelial progenitor cells derived from bone marrow and promotes new blood vessel formation. VEGF regulates all types of vascular growth, stimulates angiogenesis, and is involved in the induction of lymphangiogenesis.

Spontaneous γH2AX foci in human dermal fibroblasts in relation to proliferation activity and aging.

We assessed the effects of donor age on clonogenicity, proliferative potential, and spontaneous γH2AX foci in the proliferating (Ki67 +) and senescent (SA β-gal +) cultures of skin fibroblasts isolated from 34 donors of different age (23-82 years). Here, we demonstrated that neither the colony forming effectiveness of proliferating (Ki67+) fraction of the fibroblasts nor the average number of γH2AX foci of the same fraction does not depend on the age of the donor. The correlation between the number of γH2AX foci and the donor's age was reliable in quiescent (Ki67-) cells.

Caroli syndrome: a clinical case with detailed histopathological analysis.

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.

Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication.

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia ( ClinicalTrials.

In vitro assessment of electrospun polyamide-6 scaffolds for esophageal tissue engineering.

Artificial tissue-engineered grafts offer a potential alternative to autologous tissue grafts for patients, which can be traumatic. After decellularizing Papio hamadryas esophagus and studying the morphology and physical properties of the extracellular matrix (ECM), we generated electrospun polyamide-6 based scaffolds to mimic it. The scaffolds supported a greater mechanical load than the native ECM and demonstrated similar 3D microstructure, with randomly aligned fibers, 90% porosity, 29 μm maximal pore size, and average fiber diameter of 2.

γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation.

At high exposure levels ionizing radiation is a carcinogen. Little is known about how human stem cells, which are known to contribute to tumorigenesis, respond to prolonged radiation exposures. We studied formation of DNA double strand breaks, accessed as γH2AX and 53BP1 foci, in human mesenchymal stem cells (MSCs) exposed to either acute (5400 mGy/h) or prolonged (270 mGy/h) X-irradiation.