thymosin-beta(4) and Pressure-Ulcer

With the aging of population and the development of social economy, the incidence of chronic wounds is increasing day by day, while the incidence of burns and trauma remains at a high level, making wound repair an increasingly concerned area in clinical practice. Thymosin β4 is a naturally occurring small molecule protein in vivo, which is widely distributed in a variety of body fluids and cells, especially in platelets. Thymosin β4 has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. Thymosin β4 has been observed to promote the healing of various wounds, such as burns, diabetic ulcers, pressure ulcers. This paper will review the molecular structure, mechanism of wound healing promotion, pharmacokinetics, and clinical application of thymosin β4, aiming to introduce its potential in wound treatment and the shortcomings of current researches.. 随着人口老龄化和社会经济的发展，慢性创面发病率日益增高，同时烧创伤发病率仍处于较高水平，使得创面修复成为临床日益关注的领域。胸腺素β4是一种体内天然存在的小分子蛋白，其广泛分布于多种体液和细胞内，尤其是血小板中。胸腺素β4具有促进血管生成、抗炎、抗凋亡及抗纤维化的生物活性，在创面修复方面有许多重要的功能。目前已经在烧伤、糖尿病溃疡、压疮等多种创面中观察到胸腺素β4具有促进愈合的作用。该文将从胸腺素β4的分子结构、促创面愈合作用机制、药代动力学及临床应用方面进行综述，旨在介绍该因子在创面治疗中的潜力和当前研究的不足之处。.

Topics: Burns; Humans; Pressure Ulcer; Thymosin; Wound Healing

Thymosin β4 (Tβ4), a multifunctional peptide, has been used successfully in several clinical trials involving tissue repair and regeneration. The review will first update the current information on the common underlying cellular cascades and pathways that are basic to Tβ4's regenerative activity and second, on the current and potential uses of this protein in the clinic.. Significant advances in our understanding of the actions of Tβ4 have occurred in directing stem cell maturation and in regeneration and repair of injuries. Many of its activities directly affect the repair cascade following injury. Using PubMed, we summarize the discovery and isolation of Tβ4 as well as the studies on tissue repair, which have provided the scientific foundation for ongoing and projected trials in the treatment of eye injuries, dermal wounds, repair of the heart following myocardial infarction and healing of the brain following stroke, trauma or neurological diseases.. Based on its multifunctional activities during tissue regeneration in various animal studies, Tβ4 has the potential for new clinical applications such kidney and liver disease, as well as repair of spinal cord, bone and ligament damage. In addition, it may be useful in the treatment of a wide range of other applications, including the consequences of aging and viral infections.

Topics: Amino Acid Sequence; Animals; Epidermolysis Bullosa; Molecular Sequence Data; Pressure Ulcer; Regeneration; Spinal Cord; Thymosin; Varicose Ulcer; Wound Healing; Wounds and Injuries

Chronic nonhealing cutaneous wounds are a worldwide problem with no agent able to promote healing. A naturally occurring, endogenous repair molecule, thymosin beta 4 (Tβ4), has many biological activities that promote dermal repair. It is released by platelets at the site of injury and initiates the repair cascade. Tβ4 accelerated dermal healing of full-thickness punch wounds in various animal models, including normal rats and mice, steroid-treated rats, diabetic mice, and aged mice. Furthermore, in two phase 2 clinical trials of stasis and pressure ulcers, it was found to accelerate healing by almost a month in those patients that did heal. Tβ4 likely acts to repair and regenerate wounds by promoting cell migration and stem cell mobilization and differentiation, and by inhibiting inflammation, apoptosis, and infection. We conclude that Tβ4 is a multifunctional regenerative peptide important in dermal repair.

Topics: Animals; Clinical Trials, Phase II as Topic; Humans; Mice; Pressure Ulcer; Rats; Skin; Thymosin; Varicose Ulcer; Wound Healing

A topical combination (silvathymosin) of natural proangiogeneic protein thymosin β4 (Tβ4) and antimicrobial silver sulfadiazine was hypothesized to promote the healing of large, full-thickness, clean or infected wounds in rats. Silvathymosin showed the fastest wound healing (85%) followed by silver sulfadiazine (84%) and Tβ4 (72%). In the infected groups, the healing pattern was different, as Tβ4 and silvathymosin groups did not show similar wound healing. Wound histopathology and VEGF and KI67 immunohistochemical assessment of angiogenesis was consistent and correlated well with the tempo of healing of the acute wounds. These preliminary data demonstrate the more rapid acute wound healing properties of the combination formulation of thymosin β4 and silver sulfadiazine as compared to these agents alone. This novel agent could prove an effective treatment modality for debilitating chronic wounds and decubitus ulcers.

Topics: Animals; Anti-Infective Agents; Pressure Ulcer; Rats; Silver Sulfadiazine; Thymosin; Vascular Endothelial Growth Factor A; Wound Healing

The pathogenesis of impaired healing within pressure ulcers remains poorly characterized and rarely examined. We describe the results of a pilot study that applies matrix-assisted laser desorption/ionization imaging mass spectrometry technology for direct tissue analysis to evaluate proteomic signatures ranging from 2 to 20 kDa and phospholipids from 300-1,200 Da in focal regions within the wound microenvironment. Distinguishing molecular differences were apparent between upper vs. lower regions of ulcers and further contrasted against adjacent dermis and epidermal margins using protein profiles, ion density maps, principal component analysis and significant analysis of microarrays. Several proteins previously uncharacterized in pressure ulcers, the α-defensins (human neutrophil peptide [HNP]-1, -2, -3), are potential markers indicating whether the wound status is improving or being prolonged in a deleterious, chronic state. Thymosin β4 appears to be a favorable protein marker showing higher relative levels in adjacent dermis and maturing areas of the wound bed. Lipidomic examination revealed the presence of major lipid classes: glycerophosphocholines, glycerophosphoglycerols, glycerophosphoinositols, and triacylglycerols. Our pilot data examined from either a global perspective using proteomic or lipidomic signatures or as individual distributions reveal that imaging mass spectrometry technology can be effectively used for discovery and spatial mapping of molecular disturbances within the microenvironment of chronic wounds.

Topics: Adolescent; Adult; alpha-Defensins; Dermis; Epidermis; Female; Humans; Immunohistochemistry; Male; Middle Aged; Phospholipids; Pressure Ulcer; Principal Component Analysis; Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thymosin; Wound Healing; Young Adult

Pressure ulcers occur in up to 14% of acute hospitalizations. They cause pain, decreased quality of life, increased morbidity, and prolonged hospitalizations. Treatment includes pain control, nutritional support, relieving pressure, removing devitalized tissue, and by using dressings and medications, providing an environment in which healing can occur. Even with optimal treatment, pressure ulcers may take months to heal. Thymosin beta4 is being investigated as a treatment for pressure ulcers. Thymosin beta4 has wound healing and anti-inflammatory properties. It is thought to exert its therapeutic effect through promotion of keratinocyte and endothelial cell migration, increased collagen deposition, and stimulation of angiogenesis. A study in a rat full-thickness wound model showed that treatment with thymosin beta4 increased collagen deposition and angiogenesis and stimulated keratinocyte migration and reepithelialization. If thymosin beta4 decreases healing time, this would represent a significant advance in the treatment of pressure ulcers.

Topics: Humans; Pain; Pressure Ulcer; Quality of Life; Thymosin