# Thymosin Beta 4 Peptide(TB-500)



## johnjuanb1 (May 17, 2014)

*Animal studies with thymosin beta, a multifunctional tissue repair and regeneration peptide.*

AuthorsPhilp D, et al. Show all Journal
Ann N Y Acad Sci. 2010 Apr;1194:81-6. doi: 10.1111/j.1749-6632.2010.05479.x.

Affiliation
Abstract
*Studies in various animal models of disease and repair with thymosin beta(4) (Tbeta(4)), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. Tbeta(4) has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. *All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of Tbeta(4) in various animal models that demonstrate its potential for clinical use.


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## johnjuanb1 (May 18, 2014)

*REDUCES INFLAMMATION....*

*Thymosin beta(4) reduces lethality and down-regulates inflammatory mediators in endotoxin-induced septic shock.*

AuthorsBadamchian M, et al. Show all Journal
Int Immunopharmacol. 2003 Aug;3(8):1225-33.

Affiliation
Abstract
Thymosin beta(4) (Tbeta(4)), a highly conserved peptide with immunomodulatory properties, is the major actin-sequestering peptide in mammalian cells. Recent studies have established that Tbeta(4) can accelerate wound healing in full thickness skin wounds and following burn injuries to the cornea. In the eye studies, the accelerated healing due to Tbeta(4) was accompanied by a significant reduction in polymorphonuclear leukocyte (PMN) infiltration and a several-fold decrease in interleukin-1beta (p< or =0.015) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF1alpha, p< or =0.05). Given the recognized role of proinflammatory cytokines in septic shock and of extracellular F- and G-actin in the pathophysiology of multiple organ dysfunction, we have investigated the role of Tbeta(4) in sepsis. We report that an LD(50) dose of LPS (24 mg/kg) in rats resulted in a significant reduction of Tbeta(4) levels in the blood. Furthermore, administration of 100 microg of Tbeta(4) immediately following and at 2 and 4 h after an LD(50) dose of LPS (60 mg/kg) in mice significantly reduced mortality rates (p< or =0.024) and lowered blood levels of a number of inflammatory cytokines, eicosanoids, and other molecules that are highly elevated following endotoxin administration. In studies in human subjects given low doses of endotoxin (4 ng/kg LPS) and in patients with septic shock, we have also observed significant decreases in blood levels of Tbeta(4). The rapid disappearance of Tbeta(4) in the blood following LPS administration or during septic shock suggests that Tbeta(4) may be involved in early events leading to activation of the inflammatory cascade and ultimately the clinical sequelae of sepsis. The results of this study indicate that Tbeta(4) may have utility in the clinic in the treatment of septic shock and in syndromes associated with actin toxicities.


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## johnjuanb1 (May 18, 2014)

*REDUCES INFLAMMATION....*

*Thymosin beta(4) reduces lethality and down-regulates inflammatory mediators in endotoxin-induced septic shock.*

AuthorsBadamchian M, et al. Show all Journal
Int Immunopharmacol. 2003 Aug;3(8):1225-33.

Affiliation
Abstract
Thymosin beta(4) (Tbeta(4)), a highly conserved peptide with immunomodulatory properties, is the major actin-sequestering peptide in mammalian cells. Recent studies have established that Tbeta(4) can accelerate wound healing in full thickness skin wounds and following burn injuries to the cornea. In the eye studies, the accelerated healing due to Tbeta(4) was accompanied by a significant reduction in polymorphonuclear leukocyte (PMN) infiltration and a several-fold decrease in interleukin-1beta (p< or =0.015) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF1alpha, p< or =0.05). Given the recognized role of proinflammatory cytokines in septic shock and of extracellular F- and G-actin in the pathophysiology of multiple organ dysfunction, we have investigated the role of Tbeta(4) in sepsis. We report that an LD(50) dose of LPS (24 mg/kg) in rats resulted in a significant reduction of Tbeta(4) levels in the blood. Furthermore, administration of 100 microg of Tbeta(4) immediately following and at 2 and 4 h after an LD(50) dose of LPS (60 mg/kg) in mice significantly reduced mortality rates (p< or =0.024) and lowered blood levels of a number of inflammatory cytokines, eicosanoids, and other molecules that are highly elevated following endotoxin administration. In studies in human subjects given low doses of endotoxin (4 ng/kg LPS) and in patients with septic shock, we have also observed significant decreases in blood levels of Tbeta(4). The rapid disappearance of Tbeta(4) in the blood following LPS administration or during septic shock suggests that Tbeta(4) may be involved in early events leading to activation of the inflammatory cascade and ultimately the clinical sequelae of sepsis. The results of this study indicate that Tbeta(4) may have utility in the clinic in the treatment of septic shock and in syndromes associated with actin toxicities.


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## johnjuanb1 (May 20, 2014)

*Thymosin beta 4 induces hair growth via stem cell migration and differentiation.*

AuthorsPhilp D, et al. Show all Journal
Ann N Y Acad Sci. 2007 Sep;1112:95-103.

Affiliation
Abstract
Thymosin beta 4 is a small 43-amino-acid molecule that has multiple biological activities, including promotion of cell migration angiogenesis, cell survival, protease production, and wound healing. We have found that thymosin beta 4 promotes hair growth in various rat and mice models including a transgenic thymosin beta 4 overexpressing mouse. We have also determined the mechanism by which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth, migration, differentiation, and protease production.


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## johnjuanb1 (May 25, 2014)

*Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids.*

AuthorsYoung JD, et al. Show all Journal
Nat Med. 1999 Dec;5(12):1424-7.

Affiliation
Abstract
The possibility that glucocorticoids upregulate the expression of anti-inflammatory mediators is an exciting prospect for therapy in inflammatory diseases, because these molecules could give the therapeutic benefits of steroids without toxic side effects. Supernatants from monocytes and macrophages cultured in the presence of glucocorticoids increase the dispersion of neutrophils from a cell pellet in the capillary tube migration assay. This supernatant factor, unlike other neutrophil agonists, promotes dispersive locomotion of neutrophils at uniform concentration, lowers their adhesion to endothelial cells, inhibits their chemotactic response to fMLP and induces distinctive morphological changes. Here we show that thymosin beta4 sulfoxide is generated by monocytes in the presence of glucocorticoids and acts as a signal to inhibit an inflammatory response. In vitro, thymosin beta4 sulfoxide inhibited neutrophil chemotaxis, and in vivo, the oxidized peptide, but not the native form, was a potent inhibitor of carrageenin-induced edema in the mouse paw. Thymosin beta4 is unique, because oxidation attenuates its intracellular G-actin sequestering activity, but greatly enhances its extracellular signaling properties. This description of methionine oxidation conferring extracellular function on a cytosolic protein may have far-reaching implications for future strategies of anti-inflammatory therapy.


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## Elvia1023 (May 25, 2014)

I modified my leg training I haven't really had anymore knee issues so never bought this. Pretty much everyone I have read about using this as had great results. I am lifting much lighter in general so hopefully that will prevent any bad injuries. Although if I ever injure myself badly I will be jumping on this.


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## johnjuanb1 (May 26, 2014)

*Thymosin β4 enhances the healing of medial collateral ligament injury in rat.*

AuthorsXu B, et al. Show all Journal
Regul Pept. 2013 Jun 10;184:1-5. doi: 10.1016/j.regpep.2013.03.026. Epub 2013 Mar 21.

Affiliation
Abstract
The role played by thymosin β4 (Tβ4) in the process of wound healing was reported in several organs. However, there have been no reports that investigated the role of Tβ4 in the repair process after ligament injury. The purpose of this study was to determine whether administration of Tβ4 would improve ligament repair following injury. The medial collateral ligament (MCL) was sharply transected on the day of surgery. Then, the treatment group received 100 μL of fibrin sealant containing 1 μg of Tβ4 placed in the ligament gap. Healing tissues were evaluated by hematoxylin and eosin stain, transmission electron microscopy, and biomechanical test at 4 weeks after surgery. Histologically, healing tissues in Tβ4-treated group exhibited uniform and evenly spaced fiber bundles. However, the collagen fibers were not evenly spaced in control rats. Moreover, diameters of collagen fibrils within granulation tissue from the Tβ4-treated rats were significantly increased. In Tβ4-treated MCLs, the mechanical properties of these healing tissues were significantly higher at 4 weeks after surgery. In terms of the mechanical properties of the healing femur-medial collateral ligament-tibia complexes, the Tβ4-treated group had significantly better biomechanical properties than the control group at 4 weeks after surgery. Local administration of Tβ4 promotes the healing process of MCL, both histologically and mechanically, in a rat model. These findings provide a basis for potential clinical use of Tβ4 in repairing ligaments.


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## johnjuanb1 (May 30, 2014)

*A novel dimeric thymosin beta 4 with enhanced activities accelerates the rate of wound healing.*

AuthorsXu TJ, et al. Show all Journal
Drug Des Devel Ther. 2013 Oct 1;7:1075-88. doi: 10.2147/DDDT.S50183.

Affiliation
Abstract
OBJECTIVE: Thymosin beta 4 (Tβ4) is a peptide with 43 amino acids that is critical for repair and remodeling tissues on the skin, eye, heart, and neural system following injury. To fully realize its utility as a treatment for disease caused by injury, the authors constructed a cost-effective novel Tβ4 dimer and demonstrated that it was better able to accelerate tissue repair than native Tβ4.

METHODS: A prokaryotic vector harboring two complete Tβ4 genes with a short linker was constructed and expressed in Escherichia coli. A pilot-scale fermentation (10 L) was performed to produce engineered bacteria and the Tβ4 dimer was purified by one-step hydrophobic interaction chromatography. The activities of the Tβ4 dimer to promote endothelial cell proliferation, migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol tetrazolium), trans-well, scratch, and tube formation assays. The ability to accelerate dermal healing was assessed on rats.

RESULTS: After fermentation, the Tβ4 dimer accounted for about 30% of all the bacteria proteins. The purity of the Tβ4 dimer reached 98% after hydrophobic interaction chromatography purification. An average of 562.4 mg/L Tβ4 dimer was acquired using a 10 L fermenter. In each assay, the dimeric Tβ4 exhibited enhanced activities compared with native Tβ4. Notably, the ability of the dimeric Tβ4 to promote cell migration was almost two times higher than that of Tβ4. The rate of dermal healing in the dimeric Tβ4-treated rats was approximately 1 day faster than with native Tβ4-treated rats.

CONCLUSION: The dimeric Tβ4 exhibited enhanced activity on wound healing than native Tβ4, and the purification process was simple and cost-effective. This data could be of significant benefit for the high pain and morbidity associated with chronic wounds disease. A better strategy to develop Tβ4 as a treatment for other diseases caused by injuries such as heart attack, neurotrophic keratitis, and multiple sclerosis was also described.


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## johnjuanb1 (May 30, 2014)

Thymosin Beta 4, also known as TB500 or TB-500, is a synthetic version of the naturally occurring Peptide present in virtually all-human and animal cells, Thymosin Beta 4 (T4). It is a first-in-class candidate that promotes the following*:

WHAT THIS DOES:

1. Increases Red Blood Cells

2. Stops bleeding

3. Increase Endurance

4. Reduces Tie Up

5. Helps breathing

6. Reduces stomach acid which eliminates ulcers

7. Increases lean muscle mass

8. Helps repair tendons and ligaments


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## johnjuanb1 (Jun 1, 2014)

*Thymosin beta4 and cardiac repair.*

Shrivastava S, et al. Show all Journal
Ann N Y Acad Sci. 2010 Apr;1194:87-96. doi: 10.1111/j.1749-6632.2010.05468.x.

Affiliation
Abstract
Hypoxic heart disease is a predominant cause of disability and death worldwide. As adult mammals are incapable of cardiac repair after infarction, the discovery of effective methods to achieve myocardial and vascular regeneration is crucial. Efforts to use stem cells to repopulate damaged tissue are currently limited by technical considerations and restricted cell potential. We discovered that the small, secreted peptide thymosin beta4 (Tbeta4) could be sufficiently used to inhibit myocardial cell death, stimulate vessel growth, and activate endogenous cardiac progenitors by reminding the adult heart on its embryonic program in vivo. The initiation of epicardial thickening accompanied by increase of myocardial and epicardial progenitors with or without infarction indicate that the reactivation process is independent of injury. Our results demonstrate Tbeta4 to be the first known molecule able to initiate simultaneous myocardial and vascular regeneration after systemic administration in vivo. Given our findings, the utility of Tbeta4 to heal cardiac injury may hold promise and warrant further investigation.


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## johnjuanb1 (Jun 2, 2014)

One of Thymosin Beta 4's key mechanisms of action is its ability to regulate the cell-building protein, Actin, a vital component of cell structure and movement. Of the thousands of proteins present in cells, actin represents up to 10% of the total proteins which therefore plays a major role in the genetic makeup of the cell.


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## johnjuanb1 (Jun 2, 2014)

Thymosin Beta 4 was identified as a gene that was up-regulated four-to-six fold during early blood vessel formation and found to promote the growth of new blood cells from the existing vessels. This peptide is present in wound fluid and when administered subcutaneously, it promotes wound healing, muscle building and speeds up recovery time of muscles fibres and their cells.


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## johnjuanb1 (Jun 3, 2014)

Research confirms that T4 is a potent, naturally occurring wound repair factor with anti-inflammatory properties. T_¬®_4 is different from other repair factors, such as growth factors, in that it promotes endothelial and keratinocyte migration. It also does not bind to the extracellular matrix and has a very low molecular weight meaning it can travel relatively long distances through tissues.


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## johnjuanb1 (Jun 3, 2014)

TB-500 reduces stomach acid which helps eliminate ulcers.


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## johnjuanb1 (Jun 6, 2014)

*Thymosin beta4 increases hair growth by activation of hair follicle stem cells.
*

AuthorsPhilp D, et al. Show all Journal
FASEB J. 2004 Feb;18(2):385-7. Epub 2003 Dec 4.


Affiliation
Abstract
Thymosin beta4, a 43-amino acid polypeptide that is an important mediator of cell migration and differentiation, also promotes angiogenesis and wound healing. Here, we report that thymosin beta4 stimulates hair growth in normal rats and mice. A specific subset of hair follicular keratinocytes in mouse skin expresses thymosin beta4 in a highly coordinated manner during the hair growth cycle. These keratinocytes originate in the hair follicle bulge region, a niche for skin stem cells. Rat vibrissa follicle clonogenic keratinocytes, closely related, if not identical, to the bulge-residing stem cells, were isolated and their migration and differentiation increased in the presence of nanomolar concentrations of thymosin beta4. Expression and secretion of the extracellular matrix-degrading enzyme matrix metalloproteinase-2 were increased by thymosin beta4. Thus, thymosin beta4 accelerates hair growth, in part, due to its effect on critical events in the active phase of the hair follicle cycle, including promoting the migration of stem cells and their immediate progeny to the base of the follicle, differentiation, and extracellular matrix remodeling.


PMID 14657002 [PubMed - indexed for MEDLINE]


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## johnjuanb1 (Jun 11, 2014)

*They're busting race horses for having an unfair advantage now. Hahaha does that mean they have to sit out a certain number of races like in baseball? Hahahaha *

*Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry.*

AuthorsHo EN, et al. Show all Journal
J Chromatogr A. 2012 Nov 23;1265:57-69. doi: 10.1016/j.chroma.2012.09.043. Epub 2012 Sep 23.

Affiliation
Abstract
A veterinary preparation known as TB-500 and containing a synthetic version of the naturally occurring peptide LKKTETQ has emerged. The peptide segment (17)LKKTETQ(23) is the active site within the protein thymosin β(4) responsible for actin binding, cell migration and wound healing. The key ingredient of TB-500 is the peptide LKKTETQ with artificial acetylation of the N-terminus. TB-500 is claimed to promote endothelial cell differentiation, angiogenesis in dermal tissues, keratinocyte migration, collagen deposition and decrease inflammation. In order to control the misuse of TB-500 in equine sports, a method to definitely identify its prior use in horses is required. This study describes a method for the simultaneous detection of N-acetylated LKKTETQ and its metabolites in equine urine and plasma samples. The possible metabolites of N-acetylated LKKTETQ were first identified from in vitro studies. The parent peptide and its metabolites were isolated from equine urine or plasma by solid-phase extraction using ion-exchange cartridges, and analysed by liquid chromatography-mass spectrometry (LC/MS). These analytes were identified according to their LC retention times and relative abundances of the major product ions. The peptide N-acetylated LKKTETQ could be detected and confirmed at 0.02 ng/mL in equine plasma and 0.01 ng/mL in equine urine. This method was successful in confirming the presence of N-acetylated LKKTETQ and its metabolites in equine urine and plasma collected from horses administered with a single dose of TB-500 (containing 10mg of N-acetylated LKKTETQ). To our knowledge, this is the first identification of TB-500 and its metabolites in post-administration samples from horses.


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## johnjuanb1 (Jun 15, 2014)

*Thymosin β4 increases the potency of transplanted mesenchymal stem cells for myocardial repair.
*
AuthorsYe L, et al. Show all Journal
Circulation. 2013 Sep 10;128(11 Suppl 1):S32-41. doi: 10.1161/CIRCULATIONAHA.112.000025.

Affiliation
Abstract
BACKGROUND: Thymosin β4 (Tβ4) has been shown to enhance the survival of cultured cardiomyocytes. Here, we investigated whether the cytoprotective effects of Tβ4 can increase the effectiveness of transplanted swine mesenchymal stem cells (sMSCs) for cardiac repair in a rat model of myocardial infarction (MI).

METHODS AND RESULTS: Under hypoxic conditions, cellular damage (lactate dehydrogenase leakage), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelingc cells), and caspase-8 activity were significantly lower, whereas B-cell lymphoma-extra large protein expression was significantly higher, in sMSCs cultured with Tβ4 (1 μg/mL) than in sMSCs cultured without Tβ4, and Tβ4 also increased sMSC proliferation. For in vivo experiments, animals were treated with basal medium (MI: n=6), a fibrin patch (Patch: n=6), a patch containing sMSCs (sMSC: n=9), or a patch containing sMSCs and Tβ4 (sMSC/Tβ4: n=11); Tβ4 was encapsulated in gelatin microspheres to extend Tβ4 delivery. Four weeks after treatment, echocardiographic assessments of left-ventricular ejection fraction and fractional shortening were significantly better (P<0.05) in sMSC/Tβ4 animals (left-ventricular ejection fraction=51.7 ± 1.1%; fractional shortening=26.7 ± 0.7%) than in animals from MI (39 ± 3%; 19.5 ± 1.7%) and Patch (43 ± 1.4%; 21.6 ± 0.9%) groups. Histological assessment of infarct wall thickness was significantly higher (P<0.05) in sMSC/Tβ4 animals (50%, [45%, 80%]) than in animals from MI (25%, [20%, 25%]) group. Measurements in sMSC (left-ventricular ejection fraction=45 ± 2.6%; fractional shortening=22.9 ± 1.6%; TH = 43% [25%, 45%]), Patch, and MI animals were similar. Tβ4 administration also significantly increased vascular growth, the retention/survival of the transplanted sMSCs, and the recruitment of endogenous c-Kit(+) progenitor cells to the infarcted region.

CONCLUSIONS: Extended-release Tβ4 administration improves the retention, survival, and regenerative potency of transplanted sMSCs after myocardial injury.


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