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[Effect of "carbostimulin", vitamin D 3 and their mixture on bone tissue regeneration].

Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment. So. the content of sialic acids in blood serum normalizes on the 10th day after the operation mostly in the animals which were administered the mixture of the preparations and in which the most pronounced hypercalcemia is observed. Incorporation of 14C from NaH14CO3 into the regenerated tissue and its proteins is most intensive in the same animals.

Animals

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.

Animals

Tumor-associated phenylalanyl transfer RNA found in a wide spectrum of rat and mouse tumors but absent in normal adult, fetal, and regenerating tissues.

RPC-5 chromatography was used to examine the phenylalanyl transfer RNA (Phe-tRNA) of 25 normal rat and mouse tissues including adult, fetal, and regenerating liver; whole embryos; and other adult organs. Only a single major isoaccepting Phe-tRNA was found in every case. Phe-tRNA's from 25 transplantable rat tumors and 33 transplantable mouse tumors were similarly examined. Seventeen rat tumors and 10 mouse tumors, of a wide spectrum of histological types, were found to have an additional, tumor-associated Phe-tRNA isoacceptor. This tumor-associated Phe-tRNA was not found in the livers of animals bearing tumors that contained this isoacceptor. Differences in chromatographic behavior between the rat and mouse tumor-associated Phe-tRNA's strongly suggest that they have different structures. Our data suggest that these differences result from different degrees of incompleteness of posttranscriptional modification, most likely at the normally very hypermodified Wye (formerly called Y) base.

Animals

Seed-derived mucilage polysaccharides as biomaterials for in vivo tissue regeneration: A systematic review.

Chronic wounds, bone defects, and cartilage injuries represent persistent clinical challenges requiring biomaterial platforms that actively regulate inflammation, oxidative stress, angiogenesis, and extracellular matrix remodeling. Conventional synthetic dressings often provide limited biological activity in these contexts. Seed-derived mucilages - polysaccharide-rich hydrocolloids obtained from chia (Salvia hispanica), flaxseed (Linum usitatissimum), fenugreek (Trigonella foenum-graecum), psyllium (Plantago ovata), guar (Cyamopsis tetragonoloba), quince (Cydonia oblonga) etc. - have emerged as biocompatible, biodegradable, and chemically versatile platforms for tissue engineering. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized in vivo evidence on seed-derived mucilage-based biomaterials across wound healing, bone repair, cartilage regeneration, and related applications. PubMed, Scopus, and Web of Science Core Collection were searched for original in vivo experimental studies published in English between 2020 and 2026. Eligible studies reported at least one measurable regenerative outcome. Data were extracted independently by two reviewers, and methodological quality was assessed using the SYRCLE Risk of Bias tool. Forty-three studies were included. Hydrogels were the dominant biomaterial format, followed by films, scaffolds, sponges, nanoparticle systems, and bilayer or Janus composites. Included systems generally improved wound closure, re-epithelialization, collagen deposition, angiogenesis, antioxidant defense, and inflammatory regulation. However, most studies used small animals with short follow-up periods, and many incorporated nanoparticles or bioactive agents, limiting attribution of efficacy to the mucilage matrix alone. Risk of bias was predominantly unclear due to insufficient reporting of randomization and blinding. Blank mucilage controls, standardized characterization, long-term biosafety data, and clinically relevant models are essential prerequisites for translational progress.

Humans

Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium.

Tissue regeneration enhancer elements (TREEs) direct expression of target genes in injured and regenerating tissues. Additionally, TREEs of zebrafish origin were shown to direct expression of transgenes in border zone regions after cardiac injury when packaged into recombinant adeno-associated viral (AAV) vectors and introduced into mice. Future implementation of TREEs into AAV-based vectors as research tools and potential gene therapy modalities requires a deeper understanding of expression dynamics and potential off-target effects. Here, we applied in vivo bioluminescent imaging to mice systemically injected with AAV vectors containing different combinations of capsids, enhancers, and timing of delivery. Longitudinal tracking of expression directed by different TREEs revealed distinct amplitudes and durations of reporter gene expression in the injured heart. The liver-de-targeted AAV capsid, AAV.cc84, could deliver TREEs either pre- or post-cardiac injury to negate off-target expression in the liver while maintaining transduction in the heart. By screening AAV9-based capsid libraries dosed systemically in mice post-cardiac injury, we discovered a new capsid variant, AAV.IR41, with enhanced transduction in cardiac injuries and with elevated transduction of TREE-driven transgenes versus conventional AAV9 vectors. In vivo bioluminescence imaging offers insights into how enhancers and engineered capsids can be implemented to modulate spatiotemporal transgene expression for targeted therapies.

Animals

Ultrastructural cytology of regenerating tendon--an experimental study.

Cellular differentiations in regenerating tendon tissue of rats and guinea pigs were examined by the aid of the electron microscope. Fibroblasts with certain variations were found as basic cell types. Corresponding to the organelle composition classical fibroblasts, fibroblasts with histiocyte-like features and fibroblasts with myoide differentiations (comparable to the so-called myofibroblasts) were identified. Furthermore, proliferating capillaries with remarkable pericytic activities among other things producing fibroblast-like features must be mentioned. This fact led to the conclusion, that a part of fibroblasts in the proliferating connective tissue during tendon repair may derive from pericytes. Our ultrastructural investigations showed proof of the great plasticity of fibroblasts which function as stem cells in connective tissue regeneration.

Achilles Tendon

[Microspectrophotometric study of the lipid content in regenerating connective tissue].

An experimental quantitative histological investigation was performed to study lipids in cellular elements of the regenerated connective tissue. Flap wounds were cut on the back of white mice and granulation tissue dissected 1, 3, 7, 14 30 and 60 days after the operation was investigated. Lipids and cellular elements were revealed with Sudan III-IV black B and Nile blue. Lipid quantity was estimated by means of a modified scanning integrating microphotometer. The greatest amount of lipids in the cellular elements of the granulation tissue was revealed on the 3d day of the experiment, total optic density (TOD) of lipids in leucocytes was 0.83, TOD in histiocytes--0.6. On the 7th day the amount of lipids decreased, their TOD in leucocytes was 0.6, in histiocytes--0.4. By the 14th day only phospholipids were revealed, in histiocytes their TOD was 0.3. In subsequent days phospholipid contents continued decreasing and by the 30th day their TOD was 0.2. By the 60th day, when a scar was formed in the wound, in fact, there were no lipids in the cellular elements. The microphotometric investigation performed demonstrated qualitative and quantitative characteristics of lipids in the cellular elements of the granulation tissue in dynamics and their close dependence on the time of wound healing. It was also revealed that the regenerative process was accompanied by decreasing lipid amount in the cellular elements, and this phenomenon could be used as a peculiar test to prognosticate the process of wound healing.

Animals

Mechanical properties and hydroxyproline content of connective tissue in porous ceramic implants.

The present study describes a model applying ceramic implants (A1203) for in vivo studies of connective tissue regeneration. Two types of implants have been developed: a one-piece model for histological examination and chemical analyses, and a two-piece implant which can also be used for mechanical testing of connective tissue. When these were implanted subcutaneoulsly on the back of rats, a correlation was found between the mechanical strength and the hydroxyproline content of connective tissue in the implants. The peak synthesis occurred between the 7th and the 14th day after implantation, and a plateau was reached for both strength-increases and hydroxyproline-formation between the 14th and the 21st days. For histological examination, the implants were embedded in plastic materials and prepared as hard tissue specimens. The model presented can be applied to study connective tissue regeneration in normal and pathological conditions, including studies of the effects of various drugs on the connective tissue.

Aluminum Oxide

Matrix Metalloprotease 1 (Mmp1) promotes cell fate change for epithelial-to-epithelial transition during regeneration after radiation damage in Drosophila.

Ionizing radiation (IR) is used to treat cancer, but therapeutic failure occurs when surviving cancer cells change fate and regenerate tumors through acquired stem cell-like properties. While transcriptional mechanisms underlying cell fate plasticity have been characterized, the cellular processes enabling cell movement during tissue regeneration remain unclear. We reported previously that hinge cells of the Drosophila larval wing disc convert to pouch fate and translocate to help regenerate the pouch that suffers from more IR-induced apoptosis. We report here that IR increases the expression of extracellular proteins in the hinge, including secreted proteases and cell adhesion modulators. Functional validation using RNA interference revealed that secreted Matrix Metalloprotease 1 (Mmp1) and the related secreted protease homolog Scarface (Scaf) are required in hinge cells for IR-induced cell fate conversion and translocation. IR, we found, induces Mmp1 and scaf transcripts in hinge cells via cell-autonomous JNK signaling. Overexpression of Mmp1 specifically in the hinge was sufficient to elevate Mmp1 protein levels throughout the disc and induced cell fate change of both hinge and non-hinge cells but only in the context of irradiation. Confocal imaging in a time course demonstrated that cells undergoing fate conversion remain within the epithelial layer with little evidence for delamination or epithelial-mesenchymal transition (EMT). We propose that remodeling of the extracellular environment is a critical mechanism that enables cellular reorganization during tissue regeneration. Mmp enzymes are important for cancer biology because of their role in ECM remodeling, extracellular signaling, and EMT. Our findings demonstrate for the first time that Mmp1 is necessary and sufficient for one epithelial cell type to switch to another epithelial cell type after radiation damage. These results provide a mechanistic basis for radiation therapy-induced cell fate plasticity.

Animals

Microblasting Wound Dressings Mechanically Disrupt Polymicrobial Biofilms to Enhance Healing in Treatment-Resistant Wounds.

Treatment-resistant wounds driven by polymicrobial biofilms are a major clinical challenge, affecting millions globally and leading to chronic inflammation, persistent pain, and poor healing outcomes. These wounds are characterized by mature biofilms reinforced by dense extracellular polymeric substances, which confer strong tolerance to conventional treatments. Despite emerging technologies, such as nanoparticles, bacteriophages, and engineered enzymes, effective clearance of established biofilms remains challenging. Here, we develop a microblasting wound dressing (µBLAST) that delivers spatially confined mechano-chemical disruption at the tissue-biofilm interface to remove viscoelastic biofilm matrices and promote tissue regeneration. The µBLAST is assembled by embedding MnO2-doped diatom biosilica beneath an H2O2-releasing cellulose mesh, enabling localized catalytic microbubble generation within biofilm matrices. Confined expansion and rupture of oxygen bubbles produce localized mechanical stress sufficient to dislodge mature, antibiotic-resistant polymicrobial biofilms, while sustained H2O2 release prolongs particle activity. In a murine wound model infected with mature P. aeruginosa and methicillin-resistant S. aureus biofilms, µBLAST treatment significantly reduces biofilm burden, accelerates re-epithelialization, promotes hair regrowth, and mitigates inflammation. Moreover, µBLAST enhances antibiotic efficacy, suppressing biofilm regrowth even at ten-fold reduced drug doses. These findings highlight confined mechano-chemical biofilm disruption as a therapeutic strategy for treating mature, antibiotic-resistant biofilm infections and promoting tissue regeneration.

Biofilms

[Effect of carbostimulin and vitamin D3 on activity of glycolytic enzymes of rabbit bones, regenerates and muscles].

Activity of glycolysis enzymes such as: phosphofructokinase, aldolase, phosphoglucomutase, was determined in the regenerate of a bone, bone fragments, native bone and, for the sake of comparison, in the animal muscles after the radius resection and feeding of carbostimulin and its mixture with vitamin D3 for 10 days. On the 12th day after the radius resection the phosphofructokinase activity in rabbits increases in the native and operated bones as compared to that in bones of nonoperative animals. In the group of rabbits which were fed on the mixture of carbostimulin and vitamin D3 the phosphofructokinase activity is 7-2 times as high. In the regenerate of these animals the activity becomes 12 times as high as that in the regenerate of the control rabbits. An analogous increase in the aldolase and phosphoglucomutase reaction rate is observed in the bones of the animals which received carbostimulin and vitamin D3 (4.5 and 7.5 times, respectively). The same tendency to the increase in the activity of these enzymes is observed in the regenerate tissue. In the muscular tissue at this stage of regeneration the activity of the studied enzymes which is usually high in norm decreases.

Animals

[Electron microscopic study of the characteristics of skeletogenic tissue differentiation during distraction osteosynthesis].

Electron microscopic examination of the regenerating tissue was performed after distractional osteosynthesis carried out by the method of G. A. Ilizarov. The results showed osteogenesis to occur on the basis of the fibrous tissue formed in diastasis. The observed zones of the regeneration typical of distractional osteosynthesis are due to functional stimulation (tension) resulting in the arrangement of collagen fiber bundles and bone trabeculae in the direction of the extension forces. Cells of the skeletogenic tissue, between the bone fragments are also arranged with their longitudinal axis along the collagen fibril bundles. The ultrastructural pattern of the osteogenesis after distractional osteosynthesis reflects the intensification of the synthesis of glycosaminoglycan-protein complexes forming the main substance of the bone tissue.

Animals