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At least 55 records · Page 3Linked to original sources

PubMed1975

Epidermal downgrowths in regenerating rabbit ear holes.

Rabbits are unique among mammals in that their ears can regenerate tissues from the margins of full thickness holes which grow in and completely fill the opening in about two months. The circular blastema that forms around the edges of the hole differentiates a new sheet of cartilage as it regenerates in a centripetal direction. Similar holes in other mammals fail to regenerate and form scar tissue instead of a blastema. Histological studies of the healing around the edges of rabbit ear holes reveal that during the second week, when the epidermis is completing its migration across the wound from the opposite sides of the ear, conspicuous tongues of epidermal cells grow down into the underlying tissues at the edges of the wound. These epidermal downgrowths are situated between the original intact dermis of the skin and the more central tissues which give rise to the blastema. Such downgrowths are of a transient nature, and are no longer found once the blastema rounds up toward the end of the second week. Since they are not found in the healing of similar wounds in rabbit ears prevented from regenerating by prior removal of their cartilaginous sheets, nor in the naturally nonregenerating ears of sheep and dogs, it is considered that these downgrowths of healing epidermis may play a role in the unusual regenerative response of ear tissues in the rabbit.

Animals↗

PubMed1977

[Regeneration of the myocardium of fetuses and newborn rabbits].

The work is devoted to studies of regeneration of the myocardium in fetuses and newborns of rabbits after a mechanical trauma of the heart. It was established that in fetuses under natural conditions of the alive organism instead of the perished tissue of the myocardium during the period of 5-8 days there developed a wholesome transverse-striated musculature whose fibers contained glycogen and redox enzymes. In newborn rabbits the defect of the myocardium was replaced by a mature fibrous connective tissue, regeneration was accomplished at the expence of hyperplasia of intracellular ultrastructures. The loss by the heart muscular tissue of the capacity for complete regeneration takes place within the 24th day of the intrauterine development and the 1st day of life.

Animals↗

PubMed1977

Formation of after-cataract by regeneration of human and rabbit lens epithelium in tissue culture.

Regeneration of lens epithelium on the lens capsule was studied in tissue culture. The entire capsule with attached epithelium was taken from rabbit lenses and from human lenses with cataract. Generally, the epithelium grew in a monolayer but multilayered masses of cells were also seen. Most lens fibers degenerated during the first days and formed spherical membrane enclosed vesicles containing cytoplasm but no nuclei. The lens fiber remnants, together with regenerating epithelium, created structures that were similar in many ways to the clinical appearance of after-cataract.

Animals↗

PubMed1975

In vivo electron spin resonance in rats.

In vivo ESR studies have been made on Wistar and Sprague-Dawley rats using travelling wave helices implanted in the left lobe of the liver. Tissue regenerates completely around the Teflon-enclosed turns of the coil and histological studies have shown that it is composed of liver cells and connective tissue. Electron spin resonance studies of this tissue in vitro reported by Commoner and Ternberg in 1961 have demonstrated that it exhibits the 'tissue radical' signal. The implanted coils have detected, in vivo, a three-line spectrum due to a strong concentration of 4-hydroxy- 2,2,6,6-tetramethylpiperidine-1-oxyl free radical ('tempol'), a nitroxide spin label, injected either intramuscularly, intraperitoneally or intravenously into the experimental animal immediately prior to the measurement. They have also detected, in vivo, a similar three-line spectrum due to 'spin-labelled chlorpromazine', a tranquillizing drug to which this nitroxide spin label has been attached, injected intramuscularly or intraperitoneally into the animal immediately prior o the measurement. Work is currently in progress to increase the in vivo sensitivity of the implanted helices by menas of improved coupling techniques and the use of a time-averaging computer.

Animals↗

PubMed1977

Regeneration in the central nervous system of a pulmonate mollusc, Melampus.

The left cerebral ganglion was ablated from 72 anesthetized, adult Melampus bidentatus (Mollusca: Pulmonata). Skin incisions were well healed and normal feeding and locomotion observed four days after surgery. Dissections of animals sacrificed weekly showed that most nerves and connectives regrew within 30 days, attaching to the swollen end of the major labial nerve. The enlarged end of this nerve later developed into a distinctive bud; some of these buds contained cell bodies as soon as 42 days after surgery. As the first known report of central nervous tissue regeneration in molluscs, this study points to the need for controls in experiments involving section or ablation of nervous tissue in molluscs.

Animals↗

PubMed1977

Virus-induced lysosomal enzyme dissolution of nasal turbinate cartilage.

The mechanism of laryngotracheitis virus-induced dissolution of chick nasal turbinate cartilage was studied by lysosomal enzyme histochemistry. Five-day-old chicks were infected by intranasal instillation, and changes in lysosomal enzyme distribution were followed at daily intervals through the tissue regeneration stage, Day 28. In the mucosa the lysosomes were activated beginning on Day 1, and glycerol acid phosphatase and a diffuse form of beta-glucuronidase were released concomitant with tissue cell destruction. In the chondrocytes (where glycerol acid phosphatase was absent), beginning on Day 2, particulate (lysosomal) beta-glucuronidase decreased as diffuse beta-glucuronidase increased and extended out into the matrix. The cartilage lost its metachromatic staining properties and became soft and pliable. Regeneration of the mucosa started on Day 6 and gradual reappearance of metachromatic staining of the cartilage began on Day 8 with considerable recovery of original turbinate structure by Day 12. A lysosomal membrane labilizer, vitamin A, exacerbated the cartilage pathology, whereas a stabilizer, cortisone, retarded it.

Acid Phosphatase↗

PubMed1977

A mechanism of tumourigenesis: retrodifferentiation and reontogeny in cancer and its clinical significance.

A general theory for the origin and maintenance of the neoplastic state in tissues is presented. Cancer is described as a disease of abnormal cell and tissue differentiation, and its underlying cause is identified in the process of blocked reontogeny. Data are presented which support this hypothesis and show the striking similarities at the molecular level between neoplastic, embryonic and regenerating tissues. The hypothesis suggests that numerous potentially useful (in the clinical sense) proteins, all of them members of early development, may be associated with neoplasms. It is suggested that research aimed at extending the identification and measurement of these proteins will make a significant contribution to the clinical management of cancer and may lead to the development of easy and cheap screening techniques for the early diagnosis of neoplastic disease in man.

Alkaline Phosphatase↗

PubMed1977

[Modification of the construction and insertion of a viewing chamber for the study of microcirculation in the subcutaneous compartment of the rabbit ear].

Modification of the transparent chamber and the operation of its implantation into the tissues of the rabbit ear are described. The chamber is intended for the study of microcirculation in the subcutaneous cellular tissue of the rabbit ear. The chamber design has a number of advantages in comparison with the known models: optic characteristics are improved, assembly of the chamber is simplified, new design permits to use the regenerated tissue for further histological study. Sterilization of the chamber with gamma rays is simple and effective. The chamber is fixed in the tissues of the rabbit pinna by means of a lavsan net. An additional gluing of the latter excludes a possibility of the penetration and development of secondary infection into the operation wound and fixes the chamber in the ear tissues more firmly.

Animals↗

PubMed1975

[Influence of hormones on the functional activity of the regenerating cortex of the enucleated adrenal in situ].

The functional activity of the regenerating cortex was studied in 90 female albino rats (150-200 g) after ablation of the right adrenal and enucleation of the left one. In the period of active growth of the regenerating tissue (10 days after operation) the functional activity of parenchymatous cells was low which is evidenced by poor content of both lipids and "ketosteroids". In parallel with reparation of the adrenal adrenocortical tissue mass the content of physiologically active substances was also restored (20 days after operation). After injection of hydrocortizone (daily dosage 2,5 mg) the growth and differentiation of the bundle-reticular zone in the regenerating area was inhibited. In the glomerular zone the reactions to lipids and "ketosteroids" were mainly similar to those in the glomerular zone of intact adrenal. After injection of ACTH (daily dosage 5 or 10 mg) during 10 days the regenerating area was functionally better developed than in the control since moderately pronounced reactions to "ketosteroids" and lipids appeared in it. Fairly high content of these substances in the regenerated cortex after 20 days of injections of ACTH (10 units) as well as presence of secondary necrobiotic changes pointed to functional overstrain of the newly formed organ.

Adrenal Cortex↗

PubMed1977

Phospholipid metabolism during renal regeneration after acute tubular necrosis.

Renal function, structure, and membrane metabolism were studied during regeneration of proximal tubular cells in rats. A reversible syndrome of nonoliguric acute renal failure was induced by the intravenous administration of a low dose of mercuric chloride (1.0 mg Hg/kg). At day 1 there was a marked increase in serum urea nitrogen concentration (SUN), decrease in food intake, and a zone of proximal tubular cell necrosis in the inner cortex. By day 3 low cuboidal epithelial cells were seen, indicating that regeneration had been initiated despite decreased food intake and increasing SUN. Phospholipid synthesis for new membrane formation in regenerating cells was studied by using [14C] choline as a precursor of phosphorylcholine and cytidine diphosphocholine (CDP-choline), which are intermediates in the synthesis of renal choline-containing phospholipid. The rate of [14C]choline incorporation into phospholipids in inner cortical slices was lowest 1 day after mercury administration, then increased constantly for the next 4 days to reach a maximal value 104% above control. The rate declined slowly for the next 11 days and returned to normal by 28 days. The increased rate represented choline phosphoglyceride synthesis, since degradation was unchanged. The entire increment in choline radioactivity in regenerating tissue 2 and 3 days after mercury administration was in phospholipid or CDP-choline, which suggests that the increased number of choline molecules entering the growing cells were trapped in these two forms. The results indicate that renal regeneration is associated with a specific enhancement of the synthesis of choline-containing phospholipids. This anabolic response of the kidney occurs in the presence of systemic catabolism and progressive renal functional insufficiency.

Acute Kidney Injury↗

PubMed2026

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation.

Efficient tissue regeneration requires the precise coordination of inflammatory and regenerative programs, principally mediated by monocyte-derived macrophages. However, the transcriptional wiring and epigenomic processes behind complex macrophage subtype specification and transition between the different states are not known. Here we have identified the transcriptional repressor BACH1 as a critical, cell-intrinsic regulator of monocyte-derived macrophage specification during skeletal muscle regeneration. Using a myeloid-specific BACH1 knockout mouse model, we demonstrate that BACH1 deficiency disrupts the temporal coordination of monocyte-to-macrophage differentiation, leading to aberrant macrophage subsets with concurrent opposing pro- and anti-inflammatory features. Single-cell RNA-sequencing profiling reveals that BACH1 controls a core transcriptional network, including Nfkb1, Cebpb, and interferon signaling, governing inflammatory resolution and functional macrophage specialization. Mechanistically, BACH1 loss accelerates macrophage differentiation but also affects its core cellular identity, resulting in sustained, rather than declining inflammatory programs including upregulation of Il1b and thus, defective tissue remodeling. These immune alterations compromise the paracrine landscape during regenerative inflammation and impair muscle stem cell differentiation. Our findings establish BACH1 as a molecular tuner or controller that integrates early innate immune signaling with regenerative output, positioning it as a central node linking transcriptional control, immune fate decisions, and tissue repair.

Animals↗

PubMed2026

Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.

Inherited genodermatoses are a heterogeneous group of rare monogenic disorders. Among these, epidermolysis bullosa (EB) and ichthyoses represent paradigmatic disorders characterized by severe skin fragility and hyperkeratosis, respectively, and impaired barrier function, often with profound effects on quality of life and systemic health. Current management remains largely palliative, underscoring the urgent need for disease-modifying therapies. Over the past 2 decades, advances in epithelial stem cell biology, vector engineering and genome editing technologies have transformed the therapeutic landscape for genodermatoses. Ex vivo gene therapy has provided the first proof that genetically corrected epidermal stem cells can achieve long-term tissue regeneration in EB skin patients, establishing a new paradigm for regenerative medicine. In parallel, the emergence of programmable genome engineering platforms, including CRISPR/Cas nucleases, base editors and prime editors, have enabled increasingly precise strategies for mutation-specific correction in both recessive and dominant disorders. Furthermore, the development of in vivo topical approaches is expanding the possibility of directly targeting the skin. Despite these advances, substantial translational barriers continue to limit broad clinical implementation. Efficient and durable targeting of epidermal stem cells within a highly regenerative tissue, together with safe delivery across the skin barrier, stringent control of off-target activity, scalable manufacturing and demonstration of long-term safety, remain major challenges for the clinical translation of these approaches. In this Review, we discuss the current state of gene therapy for genodermatoses, highlighting key clinical milestones, emerging genome editing technologies and next-generation delivery systems. We further examine the biological and regulatory challenges that need to be overcome to bridge the gap between experimental innovation and clinically accessible therapies for patients with inherited skin diseases.

epidermolysis bullosa (EB)↗

PubMed1977

Control of liver size in heat-acclimated hamsters.

In the hamster, heat acclimation reduces liver weight more than it does body weight. Therefore, liver weight constitutes a lower percentage of body weight during exposure to high ambient temperature. This change is not a result of dehydration since water content of the whole body and of the liver is not altered during heat acclimation. However, changes in lactic dehydrogenase isozyme proportions indicate a higher rate of liver degradation during the first 2 wk of heat exposure. These changes are accompanied by enhancement of DNA synthesis which is found to be elevated during the early period of heat exposure and later to fall to the control levels. The enhanced DNA synthesis might be a result of a high rate of tissue regeneration which probably takes place in the organ following the commencement of the degradative processes as was suggested in partial hepatectomy. Since the activity of DNA synthesis is negatively correlated with cyclic AMP levels, it is suggested that cyclic AMP plays some role in controlling hepatic DNA synthesis during heat acclimation.

Acclimatization↗

PubMed2026

Arginine-substituted Mastoparan-C derivatives combat dual bacterial pathogens: in vitro mechanistic insights and in vivo efficacy in polymicrobial wounds.

UNLABELLED: The synergistic interactions in multi-pathogen infections compromise wound healing and limit therapeutic efficacy. In this study, we designed and synthesized arginine-substituted derivatives of the antimicrobial peptide Mastoparan-C (MP-C). Among them, Arg²MP-C and Arg4.11.12MP-C exhibited potent, broad-spectrum activity against both Escherichia coli and Staphylococcus aureus. Their enhanced antibacterial activity is associated with increased positive charge and optimized hydrophobicity. Mechanistically, both peptides employ a dual-target strategy, disrupting bacterial membranes and binding genomic DNA; Arg²MP-C acted most rapidly against the E. coli envelope, while Arg4.11.12MP-C caused the strongest membrane damage to S. aureus. In a murine polymicrobial wound model, Arg²MP-C treatment nearly achieved complete wound closure by day 10, significantly reduced bacterial loads, and promoted tissue regeneration. This study demonstrates that arginine engineering can yield peptides with potent, multi-mechanistic action, identifying Arg²MP-C as a promising candidate for combating polymicrobial wound infections. IMPORTANCE: Wounds infected with multiple bacterial species are notoriously difficult to treat, often leading to poor healing and limited effectiveness of existing therapies. In this study, we developed new antimicrobial peptides by introducing arginine substitutions into a natural peptide called Mastoparan-C. Two of our engineered peptides, Arg²MP-C and Arg4.11.12MP-C, showed potent activity against two common wound pathogens, Escherichia coli and Staphylococcus aureus. These peptides work through a dual mechanism: disrupting bacterial membranes and binding to bacterial DNA. In a mouse model of mixed-infection wounds, treatment with Arg²MP-C led to nearly complete wound closure by day 10, drastically reduced bacterial counts, and promoted tissue repair. Our findings highlight arginine engineering as a promising strategy to create next‑generation antimicrobial agents that can effectively combat complex polymicrobial wound infections, addressing a critical unmet need in clinical wound care.

Animals↗

PubMed2025

A Protocol for Detecting DNA Methylation Changes at CpG Sites of Stemness-Related Genes in Aging Stem Cells.

Aging adversely affects the self-renewal and differentiation capabilities of stem cells, which impairs tissue regeneration as well as the homeostasis. Epigenetic mechanisms, specifically DNA methylation, play a key role in the maintenance of pluripotency in stem cells and regulation of pluripotency-related gene expression. Age-related modifications in methylation patterns could influence the expression of genes critical for stem cell potency maintenance, including transcription factors Nanog and Sox2. The following chapter describes a step-by-step bisulfite sequencing protocol for detection of methylation changes in the aging stem cells and provides valuable insights into the stem cells epigenetic profile. Further, the methodology describes the steps of genomic DNA extraction, bisulfite conversion, real-time PCR amplification, and sequencing for an in-depth view of the epigenetic profile derived from aging stem cells.

DNA Methylation↗

PubMed2025

Investigating the Functions of Hox Genes Using Planarian Asexual Reproduction.

Hox genes are highly conserved developmental regulators instrumental to the formation of a wide range of diverse body plans across metazoans. While significant progress in the field of Hox gene research has been made, persistent challenges in unraveling their mechanisms of action and full repertoire of functions remain. To date, investigations of Hox gene function have been primarily conducted in research models belonging to ecdysozoa and vertebrata. Herein we summarize recent findings on Hox genes' roles in the asexual reproduction of the regenerative flatworm planaria, a member of the understudied superphylum Spiralia. We detail our optimized methods for planarian culture, gene perturbation, and induction of asexual reproduction. We aim to provide an experimentally tractable means to dissect Hox gene adult tissue functions underlying planarian asexual reproduction with broader relevance to Hox genes' established and emerging roles in regulating cellular behaviors, developmental patterning, animal behavior, and tissue regeneration.

Animals↗

PubMed1976

[Morphology of salivary gland diseases].

The human salivary glands represent a functional system with manifold responsibilities and interactions to the organism. The major and minor salivary glands show a common construction schedule consisting of an acinar functional system for the production of an enzyme- and mucin-containing primary saliva and a ductal functional system with manifold secretory, resorptive and regulatory responsibilities for the transport and the definitive composition of the saliva. The cyclic AMP and calcium iones localized in the glandular acini have an exceptional importance for the course of the secretory process. The neurohormonal control of the salivary secretion results by adrenergic and cholinergic transmitter substances. Moreover the secretory process shows a daily cycle combined with morphological alterations of the glandular cells (so called circadian structures). The fluid secretion of the salivary duct system (the output of sodium-, potassium- and chlorine-iones) represents an active energy-consumed transport process which will be regulated by several factors (autonomic nervous system, quantity of perfusion, hydrostatic pressure in the blood capillaries, transepithelial active transport by ATP-consumed pump systems). The striated ducts are the functional most important sector of the duct system for a rapid fluid- and electrolyte excretion. The terminal axons of the postganglionic sympathic and parasympathic neurits are characterized by spindle-shaped enlargements (varicosities) which contain neurosecretory granules. In the region of the acinar and intercalated duct cells a direct synaptic contact exists for the stimulation transmission, in the course of which the terminal axon contacts immediately with the effector cell by penetration of the basement membrane. The salivary glands form a part of the stabil tissues with reversible postmitotic cells in regard of the tissue regeneration. Under pathological conditions (inflammations, impediment of secretion fluid, radiation effects etc.) metaplasias and proliferations of the duct system arise with development of indifferent duct formations analogous to the type of an embryonal salivary gland. The terminal zone between intercalated and striated ducts represents an indifferent zone with large regeneratory potency. A special behaviour shows the myoepithelial cells which are developed as well to the outside of primitive embryonic duct buds as differentiated intercalated and striated ducts. Morphologically three types of diseases can be classified in the salivary glands: sialadenosis, sialadenitis and tumours.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗