Since Wnt5a expression is associated with rheumatoid arthritis and periodontitis [25, 26], expression of Wnt5a and its cell surface receptors, Frizzled and receptor tyrosine kinase-like orphan receptor 2 (Ror2), were examined. As shown in Fig 9A–9D, mRNA and protein expressions of Wnt5a and its receptors were increased by H2O2 in a time- and dose-dependent manner.
In persons with Panic Disorders (versus persons without as control) ingesting 200mg of 5-HTP, both groups experienced an increase in salivary cortisol within 3 hours but the persons with Panic Attacks continued to have greater increases after the 3 hour mark; this increased cortisol was independent of any percieved side-effects such as headache, fatigue, perspiration, nausea, etc.[43]
The scientists discovered that oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule -- ERK (extracellular signal regulated kinases) -- that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain's fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.
In the end, despite three years of intense scrutiny, the drug at the centre of the investigation remains poorly understood. In this regard, it could serve as a reflection of the whole ordeal. Everyone has an opinion, often voiced with authority and conviction. The reality is that much of this complex narrative continues to be a mystery. Many would have been well served by the humble words of the Socratic paradox – “I know that I know nothing”.

Indeed, the findings that progenitor cells of some form exist both in the regenerative zebrafish heart, and in the hearts of less-regenerative mammals supports this idea. Zebrafish have ostensibly found some method to optimize the activity of progenitor cells, perhaps either by maintaining more cells, or by harboring a more cultivating environment for regeneration. Also, both mammalian and nonmammalian hearts contain an epicardial cell layer, yet zebrafish have found some way to activate the epicardium after injury, a process linked with essential neovascularization of regenerating muscle (Lepilina et al., 2006. This result points to the adult mammalian epicardium as a potential cellular source to assist myocardial regeneration or survival. Indeed, mammalian myocardial infarcts typically show poor or insufficient neovascularization, a response that many are trying to improve experimentally. Recent findings have indicated that the G-actin sequestering protein, Thymosin-ß4, may influence the mammalian epicardium. Treatment of adult cardiac explants with Thymosin-ß4 induced the migration of fibroblasts, endothelial and smooth muscle cells as assessed by gene expression and cellular morphology (Smart et al., 2007). In addition, in vivo Thymosin-ß4 treatment could partially restore cardiac survival and function following coronary ligation (Bock-Marquette et al., 2004). Notably, Thymosin-ß4 expression is induced in the injured zebrafish heart, suggesting that fish naturally release this epicardial stimulant on injury (Lien et al., 2006).

A and B; Mouse BMMs were cultured with 200 μM H2O2 and indicated concentrations of Tβ4 peptide in the presence of M-CSF (30 ng/mL) and RANKL (100 ng/mL). C and D; PDLCs were co-cultured with mouse BMMs in the presence of M-CSF, RANKL, 200 μM H2O2, and indicated concentrations of Tβ4 peptide. To monitor osteoclast differentiation, both TRAP activity and the number of TRAP multinucleated cells were examined. * Statistically significant difference compared with control, p<0.05. The data presented were representative of three independent experiments.
It turns out oxytocin is responsible for a lot more than just love. New science has found that this amazing molecule also influences how sociable each of us is, allowing us to 'tune in' to the social information around us, perceiving it in much higher resolution. Scientists are now applying this new knowledge in the lab, and as reporter Dr Graham Phillips finds out, they're discovering oxytocin's great potential to treat social disorders, like drug addiction and alcoholism.

Affecting generosity by increasing empathy during perspective taking: In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80%, but had no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed.[89] Serious methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity.[90] Empathy in healthy males has been shown to be increased after intranasal oxytocin[88][91] This is most likely due to the effect of oxytocin in enhancing eye gaze.[92] There is some discussion about which aspect of empathy oxytocin might alter – for example, cognitive vs. emotional empathy.[93] While studying wild chimpanzees, it was noted that after a chimpanzee shared food with a non-kin related chimpanzee, the subjects' levels of oxytocin increased, as measured through their urine. In comparison to other cooperative activities between chimpanzees that were monitored including grooming, food sharing generated higher levels of oxytocin. This comparatively higher level of oxytocin after food sharing parallels the increased level of oxytocin in nursing mothers, sharing nutrients with their kin.[94]
Liver fibrosis, a major characteristic of chronic liver disease, is inappropriate tissue remodeling caused by prolonged parenchymal cell injury and inflammation. During liver injury, hepatic stellate cells (HSCs) undergo transdifferentiation from quiescent HSCs into activated HSCs, which promote the deposition of extracellular matrix proteins, leading to liver fibrosis. Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is the most abundant member of the highly conserved β-thymosin family and controls cell morphogenesis and motility by regulating the dynamics of the actin cytoskeleton. Tβ4 is known to be involved in various cellular responses, including antiinflammation, wound healing, angiogenesis, and cancer progression. Emerging evidence suggests that Tβ4 is expressed in the liver; however, its biological roles are poorly understood. Herein, we introduce liver fibrogenesis and recent findings regarding the function of Tβ4 in various tissues and discuss the potential role of Tβ4 in liver fibrosis with a special focus on the effects of exogenous and endogenous Tβ4. Recent studies have revealed that activated HSCs express Tβ4 in vivo and in vitro. Treatment with the exogenous Tβ4 peptide inhibits the proliferation and migration of activated HSCs and reduces liver fibrosis, indicating it has an antifibrotic action. Meanwhile, the endogenously expressed Tβ4 in activated HSCs is shown to promote HSCs activation. Although the role of Tβ4 has not been elucidated, it is apparent that Tβ4 is associated with HSC activation. Therefore, understanding the potential roles and regulatory mechanisms of Tβ4 in liver fibrosis may provide a novel treatment for patients.

Oxytocin production does not exist separately from the evolved neurophysiological mechanisms that regulate gonadotropin releasing hormone (GnRH) pulsatility. There are mammalian pheromones that are known to directly influence the GnRH pulse, for example androstenol. Oxytocin is not considered to be a pheromone by anyone I know who is involved in olfactory research. Sniffing it is simply a delivery method that we now can see might have negative consequences.

When you get your TB-500, it will come in a powder form. Just like BPC-157, you will need to “reconstitute” it by adding bacteriostatic water. Go back and read my article on BPC-157 to get access to a peptide calculator that will help you with the mixing/dosage math. Once your TB-500 is properly mixed, you then draw the dose into an insulin syringe, and inject it intramuscularly, subcutaneously, or intravenously (according to your preference).
Again, the three groups of mice were exposed to the stressful experience of social defeat in the cages of other more aggressive mice. This time, six hours after the social stress, the mice were put in a box in which they received a brief electric shock, which startles them but is not painful. Then 24 hours later, the mice were returned to the same box but did not receive a shock.
Tβ4 is the major monomeric actin-sequestering peptide in human tissues, and can bind globular actin (G-actin) in a 1:1 ratio and consequently involved in cytoskeletal regulation by inhibiting the polymerization of G-actin into fibrous actin (F-actin) [7]. In addition, Tβ4 is an ubiquitous naturally occurring molecule and is found at concentrations of 1 × 10−5 to 5.6 × 10−1 M in a variety of tissues and cell types, yet, no receptors for the protein have been identified [33]. A recent study suggests that internalization of exogenous Tβ4 is essential for its subsequent cellular functions [34]. Moreover, Tβ4 has been shown to be associated with, wound healing, hair growth, immunomodulation, and angiogenesis [7–9].
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RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.
These studies demonstrate that in the animal model of TBI, early (6 hours post injury) treatment with Tβ4 i.p. at doses of 6 and 30 mg/kg reduces cortical lesion volume and hippocampal cell loss and improves functional recovery, suggesting its potential as a neuroprotective therapy for TBI. More importantly, delayed (24 hours post injury) treatment with Tβ4 administered i.p. at a dose of 6 mg/kg does not reduce lesion volume but significantly improves functional outcome in rats.34 Tβ4-induced angiogenesis, neurogenesis and oligodendrogenesis may contribute to functional recovery.34 Therefore, our data suggest that promoting endogenous neurorestorative processes using Tβ4 provides a novel therapeutic option for TBI. It should be noted that systemic administration of Tβ4 is safe and well-tolerated by animals and humans.26 Further investigation of the molecular mechanisms underlying Tβ4-mediated neuroprotection and neurorestoration is warranted.
Treatment of patients with hyperbaric oxygen has been shown to improve the healing of chronic lower extremity wounds of diabetic patients (Londahl et al., 2010). In a pilot study, this treatment has been shown to more than double the number of circulating vascular stem/progenitor cells in these patients by a mechanism that elevates platelet NOS activity and to stimulate recruitment of vascular progenitor cells to wounds made in their abdominal skin (Thom et al., 2011). This treatment might be combined with topical agents for even greater efficacy in healing chronic wounds.
In 1999 researchers in Glasgow University found that an oxidised derivative of thymosin β4 (the sulfoxide, in which an oxygen atom is added to the methionine near the N-terminus) exerted several potentially anti-inflammatory effects on neutrophil leucocytes. It promoted their dispersion from a focus, inhibited their response to a small peptide (F-Met-Leu-Phe) which attracts them to sites of bacterial infection and lowered their adhesion to endothelial cells. (Adhesion to endothelial cells of blood vessel walls is pre-requisite for these cells to leave the bloodstream and invade infected tissue). A possible anti-inflammatory role for the β4 sulfoxide was supported by the group's finding that it counteracted artificially-induced inflammation in mice.
Melanotan II tanning injections have received media attention over the past few years and have been dubbed the "barbie drug" by XXXXXX. The XXXXXX website states that all products are manufactured and compounded in pharmacies in Australia and, pending the satisfactory completion of a short medical assessment, will express post products to a nominated shipping address. The XXXXXX website also states that melanotan II is defined as a 'more potent peptide' when compared to melanotan I, offering a greater density in peptide chain with noticeable results in a shorter timeframe. There are also claims of enhancing male libido, sexual performance, curing erectile dysfunction and as an appetite suppressant.
My wife has suffered from debilitating leg cramps for years, usually nocturnal. We have spent much money and time trying to find a cure, including every type of magnesium supplement we could find. Nothing has worked. We’ve also tried MSM and DMSO. Sometimes the cramps are in her calves, sometimes her thighs, sometimes her back and even her toes. Sometimes several muscles cramp at once. She has a high tolerance for pain, but these cramps leave her sobbing. I have purchased TB-500 and received it today. Does your research offer any hope that this could help eliminate her muscle spasms?
This current literature is notable for its apparent irrelevancy to an AFL footballer. It begs the question; did Tβ4 make a difference to the Essendon players? The only honest answer is that we don’t know. Most of our understanding exists on a molecular and cellular level, without any significant appreciation of how Tβ4 influences applicable outcomes such as exercise performance, endurance, muscle strength, and time to recovery. Furthermore, as the majority of research has been performed on mice, rat and pig models, any results are not directly translatable to a human, let alone an elite athlete. This is a stark contrast to a supplement such as EPO, which has been investigated thoroughly.
Oxytocin production is controlled by a positive feedback mechanism. This mechanism allows the release of the oxytocin hormone when a trigger occurs. The hormone then causes an action in the body, such as the letdown of milk or the start of labor contractions, which signals more production of oxytocin. The feedback cycle continues until the action, such as childbirth or feeding the baby, is complete.
I am not sure if my original question posted…I was wondering if I could use TB-500 to regenerate thyroid tissue? My endocrinologist said that my Hashimoto’s Thyroiditis has almost completely destroyed my thyroid. If yes, then where do I inject?? Additionally, I was wonder if the BPC-157 would have any benefits on thyroid as I plan to take orally for leaky gut/digestive issues.
Thymosin beta-4 is a naturally occurring peptide, and is found ubiquitously in our cells. A range of studies on animal models have indicated several key biological activities for Tβ4, such as “promot[ing] wound repair, tissue protection, and regeneration in the skin, eye, heart and central nervous system”. Only a handful of clinical trials in humans have attempted to explore these roles practically.

Supplements haven't been tested for safety and due to the fact that dietary supplements are largely unregulated, the content of some products may differ from what is specified on the product label. Also keep in mind that the safety of supplements in pregnant women, nursing mothers, children, and those with medical conditions or who are taking medications has not been established. You can get tips on using supplements, but if you're considering the use of 5-HTP supplements, talk with your primary care provider first. Self-treating a condition and avoiding or delaying standard care may have serious consequences.
Thymosin β4 was initially perceived as a thymic hormone. However this changed when it was discovered that it forms a 1:1 complex with G (globular) actin, and is present at high concentration in a wide range of mammalian cell types.[11] When appropriate, G-actin monomers polymerize to form F (filamentous) actin, which, together with other proteins that bind to actin, comprise cellular microfilaments. Formation by G-actin of the complex with β-thymosin (= "sequestration") opposes this.
Tβ4 is a multifunctional regenerative small peptide containing 43-amino acids, and it is the major G-actin-sequestering molecule in eukaryotic cells.21 Tβ4 has pro-survival and pro-angiogenic properties, protects tissue against damage, and promotes tissue regeneration.22,23 It also plays a key role in corneal, epidermal and cardiac wound healing.21 Tβ4 participates in axonal path-finding, neurite formation, cell proliferation, and neuronal survival.24-26 Our previous studies show that Tβ4 reduces inflammation and stimulates remyelination and improves functional recovery in animal models of experimental autoimmune encephalomyelitis (EAE) and stroke.25,27 In summary, these pleiotropic properties make Tβ4 an ideal candidate for treatment of TBI.
In 1999 researchers in Glasgow University found that an oxidised derivative of thymosin β4 (the sulfoxide, in which an oxygen atom is added to the methionine near the N-terminus) exerted several potentially anti-inflammatory effects on neutrophil leucocytes. It promoted their dispersion from a focus, inhibited their response to a small peptide (F-Met-Leu-Phe) which attracts them to sites of bacterial infection and lowered their adhesion to endothelial cells. (Adhesion to endothelial cells of blood vessel walls is pre-requisite for these cells to leave the bloodstream and invade infected tissue). A possible anti-inflammatory role for the β4 sulfoxide was supported by the group's finding that it counteracted artificially-induced inflammation in mice.

We had previously reported that successful hunters experienced a surge in testosterone that lasted from the moment they made a kill until their return home – a “winner effect,” rewarding them for their work. Testosterone reinforces the hunting activity and simultaneously helps with muscle regeneration afterwards - similar to the elated feeling we might have after doing sports or other exercise.
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For example, when a mother is nursing her baby, that stimulation from the breast is going into the brain and causing those oxytocin neurons to fire and release oxytocin directly into the brain. That's much more powerful than what happens with a nasal spray. So I think that, you know, in the future, we may have these drugs that can, in a very potent way, tap into this oxytocin system to treat many different kinds of disorders.
When combined with antidepressants of the MAOI or SSRI class, very high parenteral doses of 5-HTP can cause acute serotonin syndrome in rats.[23][24] It is unclear if such findings have clinical relevance, as most drugs will cause serious adverse events or death in rodents at very high doses. In humans 5-HTP has never been clinically associated with serotonin syndrome, although 5-HTP can precipitate mania when added to an MAOI.[25]
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