Repair and Recovery Research

Thymosin-β4, and Human Vitronectin peptides Grafted to Collagen Tune Adhesion or VEGF Gene Expression in Human Cell Lines

Collagen is the most abundant protein in the human body, found in the bones, muscles, skin, and tendons. It provides structural support to the extracellular space of connective tissues. Due to its rigidity and resistance to stretching, it is the perfect matrix for skin, tendons, bones, and ligaments.

Researchers wanted to test the modulation of adhesiveness strength and specificity of collagen scaffolds through the grafting of adhesive peptides. They thought that this may improve both cell adhesion and migration, favoring the tissue regenerative process. However, to date, no such study has been performed.

More specifically, in the study, researchers examined thymosin-β4 (Tβ4P) and Human Vitronectin (HVP) (seen in the image to the right) derived peptides grafted to collagen by thiolene Michael addition in order to improve collagen bioactivity for regenerative medicine approaches.

Tβ4P and HVP are known to exert proangiogenic and proadhesive activity respectively, and HVP is involved in osteogenesis promotion. The ability of these peptides to increase collagen cell adhesion and angiogenesis properties is assessed on human cell lines. See image below showing the peptides grafting strategy to collagen coatings.

How Does BPC 157 Work?

BPC 157 is a derivative of a natural protein called body protection compound (BPC). BPC was first isolated from the digestive system where it plays an important role in protecting the stomach lining from stomach acid. Research has since revealed that the healing properties of BPC 157 extend well beyond the gut. The peptide has been shown to boost wound healing in a variety of tissues, increase the rate of blood vessel growth, improve blood clotting, and enhance the immune system.To understand how BPC 157 can have such wide-ranging effects, it is necessary to start at the most basic level of its activity to see how its properties build upon one another to create an excellent healing peptide.

How Does BPC 157 Work in Blood Vessels?

Research shows that BPC 157 works in two different ways in blood vessels. First, it helps blood vessels to relax so that blood flows more easily through them. It does this by increasing concentrations of a natural compound called nitric oxide. Nitric oxide is critical to not just maintaining blood pressure, but to maintaining the health of the endothelial cells that line blood vessels. (11)

Ac-SDKP is a Peptide Fragment of Thymosin Beta 4 (TB-500)

“Tβ4 is a naturally occurring peptide consisting of 43 base pairs of amino acids and generates the N-terminal tetrapeptide AcSDKP.” (14)

Peptide Ac-SDKP was isolated from the whole Thymosin Beta 4 Peptide Sequence.

Ac-SDKP Reduced Kidney Fibrosis.

“Treatment of cultured cells with ACEi alone or in combination with AcSDKP prevented the downregulated expression of miR-29s and miR-let-7s induced by TGFβ stimulation. Interestingly, ACEi also restored miR-29 and miR-let-7 family cross-talk in endothelial cells, an effect that is shared by AcSDKP suggesting that AcSDKP may be partially involved in the anti-mesenchymal action of ACEi. The results of the present study promise to advance our understanding of how ACEi regulates antifibrotic microRNAs crosstalk and DPP-4 associated-fibrogenic processes which is a critical event in the development of diabetic kidney disease.” (14)

BPC 157 Arginate vs BPC 157 Acetate

Another way to evaluate the quality of a BPC 157 source is to look at whether the seller understands the difference between the arginate and acetate versions of the peptide. BPC 157 acetate is a slightly modified version of the natural peptide that provides for increased shelf-life and better resistance to the extremes of shipping environments. BPC 157 acetate is commonly used for subcutaneous injection as it is degraded in the GI tract to such an extent that nearly 98% of it is gone after just a short time in gastric acid.For researchers interested in understanding the effects of oral administration of BPC 157, then the arginate salt is preferred. BPC 157 arginate retains the superior shipping and storage properties of BPC 157 acetate, but is also stable in gastric acid for extended periods. Research shows that just 10% of BPC 157 arginate is degraded after 5 hours in gastric acid.BPC 157 arginate is sometimes referred to as “stable BPC 157.” This is a correct usage of the term stable, but it is important for anyone looking to buy BPC 157 that they specify whether the seller is referring to BPC 157 arginate or acetate as the two peptides are both “stable” depending on context.

What Is BPC 157?

If you are looking to purchase BPC 157, you likely already know what the peptide is and the research that has been done on it. Still, it is important to cover this topic broadly so that you can evaluate whether the BPC 157 source you are considering buying BPC 157 from is reliable or not.

BPC 157 is a synthetically produced peptide based off of the naturally occurring body protection compound (BPC) protein that was isolated from human gastric contents. This short peptide has been shown to have both anti-inflammatory and wound healing effects not just in the gastrointestinal system, but in musculoskeletal and neurological tissue as well. BPC 157 also promotes the growth of blood vessels and is thought to help maintain homeostasis.

Research on BPC 157 has focused primarily on its wound healing properties. It has undergone phase 1 clinical trials and has been investigated as a potential treatment for tendon injury, inflammatory bowel disease, and accelerating the rate of fistula healing.

What is Thymosin Beta-4?

The beta-thymosins (b-thymosins) comprise a family of structurally related, highly conserved amino acid sequences in species ranging from mammals to echinoderms. Of the 16 known family members, thymosin β4 (Tb4), thymosin β10 (Tb10), and thymosin β15 (Tb15) are found in man.

Thymosin beta-4 (TB4) is a 43 amino acid, 5kDa polypeptide that is an important mediator of cell proliferation, migration, and differentiation. TB4 is the most abundant member of the β- thymosin family in mammalian tissue and is regarded as the main G-actin sequestering peptide. It is found in all tissues and cell types except red blood cells. Thymosin beta-4 is angiogenic and can promote endothelial cell migration and adhesion, and angiogenesis. TB4 also accelerates wound healing and reduces inflammation and scarring when applied in dermal wound-healing assays.

Beta thymosins bind and sequester monomeric actin, thus preventing actin polymerization and formation of filamentous actin. Actin is a vital component of cell structure and movement. Actin is involved in many important non-muscle cellular processes, including cell locomotion, chemotaxis, phagocytosis, and cytokinesis. Of the thousands of proteins present in cells, actin makes up to 10% of the total proteins in a cell, representing a major role in the genetic makeup of the cell.

Animal studies of disease and repair when using thymosin beta-4, the major actin-sequestering molecule in mammalian cells, have provided a base for the ongoing multicenter clinical trials for wound healing, including dermal, corneal, and cardiac. TB4 has 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.

Thymosin beta-4 also inhibits inflammation, microbial growth, scar formation (by reducing the level of myofibroblasts), and apoptosis, and protects cells from cytotoxic damage, including glutamate neuronal toxicity. In addition, it binds to G-actin, blocks actin polymerization, and is released with factor X by platelets. These activities contribute to the multiple wound healing properties that have been reported in animal and human studies.

Peptides for Tendon Repair Research

Tendon injuries are incredibly common, not just among athletes, but in the general population. Commonly injured tendons include the Achilles and biceps tendon as well as tendons of the hands and feet. Unlike most illnesses and injuries, however, tendon injuries are more common among the young than the old. This is counterintuitive, especially given that the cause of these injuries is cumulative degeneration followed by sudden excess loading. Few of tendon injuries are caused by systemic disease or a genetic disorder.The incidence of tendon-related injuries is on the rise, increasing almost 140% between 2012 and 2016[1]. The increase is attributed to greater amateur athletic participation, but also has roots in high rates of on-the-job injuries. For these reasons, and many others, peptides for tendon repair research have become a hot topic. Here is a look at what the state of the art is in the field of peptides for tendon repair research.

How Do Tendons Heal?

Tendons connect muscle to bone and transfer all the energy from a muscle contraction to the bones that provide structure and support. Unfortunately, tendons can be cut, bruised, sprained, or ruptured in a variety of ways. Tendon ruptures are serious and can take anywhere from four to eighteen months to heal and almost always require surgery. Even tendonitis, which is just inflammation due to minor damage, can take upwards of four months to heal.

Unfortunately, injured tendons are at higher risk of re-injury, generally because the healing process is not as orderly as when a tendon is originally formed. Tendons are not designed to regenerate, but rather are meant to last a lifetime without much change. As such, they do not possess the kind of regenerative properties (e.g., abundant stem cells) that tissues like the GI tract or skin do. What is worse, the rate at which a tendon can heal, even if the healing is limited, is almost always outpaced by the rate at which we can cause injury to it. In other words, tendon injury tends to accumulate and the more active you are, the more likely you are to experience a large-scale tendon failure.

Under the healing process, tendons first become inflamed, an immune response that causes pain and limits mobility. This stage, however, is slow to resolve because of the tendon’s poor blood supply. Eventually, however, healing gives way to the repair phase in which cells like fibroblasts proliferate and start replacing damaged tissue. This stage then gives way to remodeling, which is carried out by stem cells and various other cells. Once again, the relative dearth of nutrient supply to the tendon limits the effectiveness of these stages and accounts for the very slow rate at which tendons heal.

BPC 157 is a peptide that has demonstrated anti-inflammatory, cytoprotective, and endothelial-protective effects in different organ systems in different species. BPC 157 activated endothelial nitric oxide synthase (eNOS) is associated with nitric oxide (NO) release, tissue repair and angio-modulatory properties which can lead to improved vascular integrity and immune response, reduced proinflammatory profile, and reduced critical levels of the disease. As a result, discussion of its use as a potential prophylactic and complementary treatment is critical.

Figure 2: BPC 157 Molecule

Researchers hypothesize BPC 157 to be a promising future treatment for COVID-19 patients. Plausibly, BPC 157 may offer improved COVID-19 outcomes by mitigating cytokine derailment and subsequent multi-organ failure based on its anti-inflammatory, cytoprotective, and endothelium-protecting effects (e.g., through BPC 157-eNOS interactions). Furthermore, BPC 157 applications may obstruct viral replication, improve clinical and biochemical parameters, attenuate organ damage from the systemic alterations, provoked from SARS-CoV-2. Support for such a hypothesis is explained in further detail below.

BPC-157 is a partial form of the protein known as body protection compound (BPC). BPC is a natural component within the body and has been found, in experiments on animals, to promote healing. BPC is not just active in intestinal repair and healing, but appears to produce similar effects in a number of tissues. Scientific studies based on animal test subjects has shown that its healing actions are at least partially linked to growth hormone (GH).

Dementia Overview

Dementia is a chronic and progressive brain disorder that affects a person’s cognitive abilities, including memory, thinking, behavior, and communication. It is a broad term used to describe a range of symptoms caused by a variety of underlying diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others. Furthermore, Alzheimer’s disease is a type of dementia that is characterized by a gradual and irreversible decline in cognitive abilities, including memory, language, perception, and reasoning. It is the most common cause of dementia, accounting for 60-70% of all cases.According to the World Health Organization (WHO), there are an estimated 50 million people worldwide living with dementia, and this number is expected to triple by 2050. Dementia is more common in older adults, but it can also affect younger people, especially those with genetic predispositions or other risk factors. Alzheimer’s disease is responsible for 60-80% of these cases. In the United States alone, over 6 million people are living with Alzheimer’s disease, and this number is expected to rise to nearly 14 million by 2050.

TB4 Mechanism of Action

The mechanism of action of thymosin-beta 4 is multifaceted and complex. This peptide is involved in many essential biological processes, including tissue repair, wound healing, and angiogenesis. In the context of neurocognitive disorders, thymosin-beta 4 has been shown to have several potential mechanisms of action that may help improve brain function and alleviate symptoms of diseases such as dementia and Alzheimer’s.

One of the primary ways in which thymosin-beta 4 may help with neurocognitive issues is by promoting the growth and regeneration of neurons in the brain. Studies have shown that thymosin-beta 4 can stimulate the formation of new neurons and support the survival of existing neurons, which can lead to improved cognitive function.

Thymosin-beta 4 has also been found to have anti-inflammatory and antioxidant properties, which may be beneficial in the context of neurocognitive disorders. Inflammation and oxidative stress are known to contribute to the development and progression of these diseases, and thymosin-beta 4 may help reduce their impact on the brain. Additionally, thymosin-beta 4 has been shown to improve the function of microglia, immune cells in the brain that play a critical role in maintaining brain health. Microglia help clear out damaged cells and debris, but they can also contribute to inflammation and damage in certain contexts. Thymosin-beta 4 appears to help regulate microglia function and reduce their harmful effects, which may be beneficial in the context of neurocognitive disorders.

The potential mechanisms of action of thymosin-beta 4 in the context of neurocognitive disorders are diverse and complex, but the evidence suggests that this peptide has the potential to improve brain function and alleviate symptoms of diseases such as dementia and Alzheimer’s. Please see the very exciting research examples below as to how this peptide could benefit those with the diseases.

NAD+ is the second most abundant cofactor in the human body. Anti-aging therapies are becoming more mainstream as aging is now more often being viewed as a disease. Now that this transition is happening, the ability for NAD+ to activate PARPS, Sirtuins, and help with immune dysregulation has been thoroughly investigated and NAD+ and its precursors have been highly popularized. The clinical importance of maintaining cellular NAD+ levels was established early in the last century with the finding that pellagra, a disease characterized by diarrhea, dermatitis, dementia and death, could be cured with foods containing the NAD+ precursor niacin.

Additionally, cellular concentrations of NAD+ have been shown to decrease under conditions of increased oxidative damage such as occur during aging Altered levels of NAD+ have been found to accompany several disorders associated with increased oxidative/free radical damage including diabetes, heart disease, age-related vascular dysfunction, ischemic brain injury, misfolded neuronal proteins, and Alzheimer’s dementia. Interventions targeted at restoring NAD+ has been shown in animal models to support healthy aging and improve metabolic function, and dementia.

A need for NAD+ in muscle development, homeostasis, and aging

In a review study, researchers discuss the recent data that document conserved roles for NAD+ in skeletal muscle development, regeneration, aging, and disease as well as interventions targeting skeletal muscle and affecting NAD+ that suggest promising therapeutic benefits. The researchers also highlight gaps in our knowledge and propose avenues of future investigation to better understand why and how NAD+ regulates skeletal muscle biology.