To determine the direct effect of Tβ4 peptide on osteoclastogenesis, mouse BMMs were directly exposed to Tβ4 peptide. Direct treatment with Tβ4 peptide also reduced the number of multinucleated TRAP-positive cells and TRAP activity in a dose-dependent manner (Fig 7A and 7B). Since Tβ4 downregulated H2O2-induced various cytokines expression, the indirect effect of Tβ4 on osteoclast formation through PDLC cells using co-culture system were investigated. After addition of Tβ4 peptide to the BMMs-PDLCs co-culture, the number of osteoclast and TRAP activity were also significantly decreased (Fig 7C and 7D).
 Don't be surprised.  A lot of people haven't heard of Melanotan.  Melanotan is a tanning peptide that stimulates the production of melanin in the body to foster a deep, natural tan.  This is the body's way of protecting itself from too much sun exposure by increasing the level of melanin in the body.  Melanin is your body's natural response to UV damage.  The end result is a darkening of the skin.
The relationship between oxytocin and human sexual response is unclear. At least two non-controlled studies have found increases in plasma oxytocin at orgasm in both men and women.[5][6] The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.[5] Murphy et al. (1987), studying men, found that oxytocin levels were raised throughout sexual arousal and there was no acute increase at orgasm. [7] A more recent study of men found an increase in plasma oxytocin immediantly after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted that these changes "may simply reflect contractile properties on reproductive tissue."[8]
Recent reports have stated that inhibitors of Wnt signaling have emerged as promising strategies for bone disease and inflammatory diseases [26, 55]. Wnt5a, one of the most common Wnt molecules that activate the non-canoical pathway, binds to Fzd and its co-receptor, Ror2 [56]. In synoviocytes from rheumatoid arthritis patients, the expressions of Wnt5a and Frizzled5 (Fzd5) were significantly enhanced [25] and their blockades inhibited synoviocyte activation [55]. Recently, Wnt5a was highly expressed in synovial tissues in a mouse model of rheumatoid arthritis where inhibition of Wnt5a-Ror2 signaling suppressed bone loss [57]. Our data demonstrated that ROS up-regulated Wnt5a and its cell surface receptors, Frizzled and Ror2, as well as mRNA and protein expressions in time- and dose-dependent manners in PDLCs.
“This is a very ancient molecule,” says Sue Carter, a neuroscientist at Indiana University in Bloomington, whose lab pioneered many of the early studies of oxytocin in voles. “It has been used and reused for many purposes across the evolution of modern animals, and almost everybody who's tried to look at an effect of oxytocin on anything like social behaviour has found something.”

TB-500 is a synthetic fraction of the protein thymosin beta-4, which is present in virtually all human and animal cells. The main purpose of this peptide is to promote healing. It also promotes creation of new blood and muscle cells. The healing effects of TB-500 have been observed in tendons, ligaments, muscle, skin, heart, and the eyes. Thymosin beta-4 is naturally produced in higher concentration where tissue has been damaged. This peptide is also a very potent anti-inflamatory agent. 

FGF-2 and VEGF enhance angiogenesis in chronic wounds (Greenalgh, 1996; Kirchner et al., 2003). Thymosin β-4 increases angiogenesis, consistent with its ability to induce epicardial cells to differentiate into endothelial and smooth muscle cells of coronary vessels (Chapter 7). L-arginine enhances angiogenesis in chronic wounds by enhancing the production of endothelial nitric oxide and improving blood flow (Shi et al., 2003). L-arginine also plays a role in the formation of proline, which is essential for the structure of collagen molecules. ChrysalinTM, a synthetic peptide representing the portion of human thrombin that binds to the surface of endothelial cells, doubled the incidence of complete healing of diabetic foot ulcers in human patients (Fife et al., 2007). Another molecule used to treat peripheral artery disease, pentoxifylline, was reported to improve blood flow in chronic wounds by reducing blood viscosity (Falanga et al., 1999).
Jump up ^ Carlier MF, Hertzog M, Didry D, Renault L, Cantrelle FX, van Heijenoort C, Knossow M, Guittet E (September 2007). "Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module". Annals of the New York Academy of Sciences. 1112: 67–75. Bibcode:2007NYASA1112...67C. doi:10.1196/annals.1415.037. PMID 17947587.
The vascular system in the normal adult brain is stable, but is activated in response to certain pathological conditions including injuries.68 Von Willebrand factor (vWF) staining has been used to identify vascular structure in the brain after TBI.69 TBI alone significantly increased vascular density in the injured cortex, CA3, and DG of the ipsilateral hemisphere when examined at day 35 after TBI compared to sham controls.18,34,64,65 Tβ4 treatment significantly increased the vascular density in these regions compared to saline treatment.34 This is in agreement with in vitro and in vivo pro-angiogenic effect of Tβ4.70,71
The need to balance hunting pride and social obligations, and the necessity to reconnect with a family that depends on their provisioning were likely experienced by men throughout much of human evolutionary history. Oxytocin is found in all mammals and originated in the mother-infant bond, where it helps with childbirth, nursing and bonding. In some species, this existing hormonal mechanism could then be harnessed for novel contexts – for instance, men investing in pair-bonding and family provisioning, which is rare among mammals.
Silencing of the Tβ4 or Wnt5a gene was achieved by transfecting cells with small interfering RNA (siRNA). Cells were transfected with Tβ4 or Wnt5a siRNAs (30 nM) for 24 hours using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. Cells were transfected with Silencer negative control siRNA using the same protocol.
In a landmark 1979 study3, Cort Pedersen and Arthur Prange at the University of North Carolina in Chapel Hill showed that giving oxytocin to virgin rats could trigger maternal behaviours: the animals would build nests, lick or crouch over unfamiliar pups and even return lost pups to the nest. Researchers went on to show that oxytocin signalling in the brains of prairie voles (Microtus ochrogaster) helps the animals to form lifelong pair bonds4 — a rarity among mammals. In 2012, researchers even found a version of oxytocin in the tiny roundworm Caenorhabditis elegans, where it helps the animals find and recognize mates5.
Thymosin beta-4 (Tβ4) is a water-soluble, 43-amino acid, and 4.9 kDa protein that was originally isolated from bovine thymus [6]. Since Tβ4 is the major actin-sequestering molecule in eukaryotic cells and is found in all cells [7], Tβ4 has multiple diverse cellular functions, including tissue development, migration, angiogenesis, and wound healing [7]. We previously reported that Tβ4-overexpressing transgenic mice, using a construct on the skin-specific keratin-5 promoter, have abnormal tooth development and enhanced stimulation of hair growth [8]. Moreover, exogenous Tβ4 has anti-inflammatory effects in the bleomycin-induced mouse model of lung fibrosis [9], tooth extraction sockets in rats [10], rat model of myocardial ischemia [11], corneal wound healing [12], wound healing of rat palatal mucosa [13], in vitro model of cultured human gingival fibroblasts [14], and cardiac fibroblasts [15]. However, the effects of Tβ4 over expression or inhibition on differentiation are controversial. Exogenous β4 peptide inhibited osteogenic differentiation but facilitated adipogenic differentiation in human bone marrow-derived-mesenchymal stem cells (MSCs) [16]. In contrast, Tβ4 inhibition by Tβ4 siRNA attenuated odontoblastic differentiation in the odontoblast-like cells, MDPC-23 [17]. Moreover, we recently demonstrated that odontoblastic differentiation was enhanced by activation of Tβ4 by Tβ4 peptide but was decreased by Tβ4 siRNA in human dental pulp cells (HDPCs) [18]. However, the effects of Tβ4 on osteoclastic differentiation have not been reported.
Cells that line blood vessels (endothelial cells), taken from human umbilical chord veins, were grown in culture and the layer of cells subjected to a scratch wound. Cultures were then treated with Tb4 or kept in growth medium without Tb4. When examined four hours later, Tb4 treatment attracted cells to migrate into the wound and accelerated their movement, showing it is a chemoattractant. Cell migration was four to six times faster in the presence of Tb4 compared to the migration of untreated cells. Tb4 also hastened wound closure and increased the production of enzymes, called metalloproteases, that could pave the way for angiogenesis by breaking down barrier membranes and facilitating the invasion of new cells to the needy area, to form new vessels. Other experiments showed Tb4 acts in vivo. When endothelial cells were implanted under the skin in a gel supplemented with Tb4, the cells formed vessel-like structures containing red blood cells, indicating the ability to stimulate angiogenesis in the animals.
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.
Jump up ^ Hicks C, Ramos L, Reekie T, Misagh GH, Narlawar R, Kassiou M, McGregor IS (June 2014). "Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats". British Journal of Pharmacology. 171 (11): 2868–87. doi:10.1111/bph.12613. PMC 4243861. PMID 24641248.
Hey Adrian, thanks for reaching out. Firstly, I am not a doctor and nothing I say should be taken as medical advice. For something like this I suggest you book a consult at
Evidence accumulated over the past decades has overturned the traditional dogma that the adult mammalian brain cannot generate new neurons. Adult neurogenesis has been identified in all vertebrate species examined thus far including humans.44-49 Newly generated neuronal cells originate from neural stem cells in the adult brain. Neural stem cells are the self-renewing, multipotent cells that generate the neuronal and glial cells of the nervous system.50 The major function of neurogenesis in adult brain seems to replace the neurons that die regularly in certain brain areas. Granule neurons in the DG continuously die and the progenitors in the subgranular zone of the DG may proliferate at the same rate as mature neuronal death to maintain a constant DG cell number.51 Similarly, the newly proliferated cells from the subventricular zone migrate and replenish the dead olfactory bulb neurons.52 Here, we focus on DG neurogenesis which is important for spatial learning and memory. In normal adult rats, newborn neural cells migrate from the subgranular zone of the DG of the hippocampus into the granule cell layer and eventually become mature granule neurons.53 These new granule neurons extend axonal processes to their postsynaptic targets54-57 and receive synaptic input.58 TBI stimulates widespread cellular proliferation in rats and results in focal neurogenesis in the DG of the hippocampus.59,60 Some of the newly generated granule neurons integrate into the hippocampus. The integration of the injury-induced neurogenic population into the existing hippocampal circuitry coincides with the time point when cognitive recovery is observed in injured animals.44
Few forms of trust are more basic than that between a newborn and its mother. Scientists have discovered that this relationship is strengthened by the hormone oxytocin, released when the baby stares up at mom while breast feeding. Staring lovingly at your boyfriend or girlfriend can trigger their release of oxytocin too, as can warm physical contact like touching and hugging. (Levels increase during sex and peak at orgasm, which may help explain the age-old question “But will you love me in the morning, when your oxytocin levels have dropped?”) Oxytocin reduces stress in arguing couples, helps us recognize faces, even helps us look at a face (in fact, just a pair of eyes) and identify the mood that person is in. The stuff is magic.
Oxytocin is relatively safe when used at recommended doses. Potential side effects include: Central nervous system: Subarachnoid hemorrhage, seizures; Cardiovascular: Increased heart rate, blood pressure, systemic venous return, cardiac output, and arrhythmias;Genitourinary: Impaired uterine blood flow, pelvic hematoma, tetanic uterine contractions, uterine rupture, postpartum hemorrhage.
In 19 obese females given either placebo or 8mg/kg (weight not actually given, only BMI between 30-40 for women) daily for 5 weeks without any concurrent dietary recommendations, 5-HTP treatment was associated with a decrease in appetite and food intake (resulting in weight loss) without significantly affecting mood state.[9] This study noted that food intake was reduced from an average of 2,903kcal to 1,819kcal (62% of baseline) while placebo only reduced calories to 80%, and the 0.5kg weight loss in placebo was outperformed by a near 1.5kg loss in 5-HTP. These weight loss effects have been noted with 750mg 5-HTP over 2 weeks in overweight diabetics[10] and over 12 weeks in obese persons given 900mg 5-HTP daily (58% of baseline intake); this latter study had a 6 week trial without a diet (in which significant weight loss was only noted at week 6) followed up by coadministration with a diet where weight loss proceeded to reach an additional 3.3kg over the subsequent 6 weeks;[11] this latter study is duplicated in Medline.[12]

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]

Melanotan II was originally developed as a treatment for sexual dysfunction. However, this was abandoned when the metabolite bremelanotide was developed instead for treatment of haemorrhagic shock. Melanotan II is usually injected subcutaneously for the purposes of sunless tanning, appetite suppression, inducing sexual desire and penile erection and other conditions such as rosacea and fibromyalgia. There are also dose forms available for nasal administration. The therapeutic dose is considered to be 0.01 mg/kg.
Loading is not absolutely necessary, it is only done to achieve results faster. Loading means taking doses more frequently to build up initial tan faster thus getting in tan maintenance mode sooner. Typical loading is done by taking 0.5mg once a day until desired skin tone is achieved. Loading dose can slightly vary from person to person, depending on skin type, bodyweight and other factors, but 0.5mg is pretty standard for most
Studies demonstrate that TB-500 is a potent, naturally occurring wound repair factor with anti-inflammatory properties. Tß4 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. One of TB-500 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.
Jump up ^ Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H (March 2010). "Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 153B (2): 629–39. doi:10.1002/ajmg.b.31032. PMID 19777562.
TB-500 is a synthetic version of the naturally occurring peptide present in virtually all human and animal cells, Thymosin Beta-4. This potent peptide is a member of a ubiquitous family of 16 related molecules with a high conservation of sequence and localization in most tissues and circulating cells in the body. TB-500 not only binds to actin, but also blocks actin polymerization and is the actin-sequestering molecule in eukaryotic cells.
Affecting generosity by increasing empathy during perspective taking. In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80% but has no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experimental explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.13

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.
Don’t take it by itself, you want to take it with a meal. The half life seems to vary; some people just need to take a single dose daily whereas some break it up into several doses. The dosage range is pretty wide, from 50 to 900 milligrams. Many report the antidepressant effect desired from lower doses, so start low with this one. Do not use a liquid form of 5-HTP.
Cells were incubated with 200 μM H2O2 for indicated times (A). Cells were pretreated with indicated concentrations of Tβ4 peptide (0.1–5 μg/mL) for 2 hours and then incubated with 200 μM H2O2 for 60 minutes (B). Data were representative of three independent experiments. The bar graph shows the fold increase in protein expression compared with control cells * Statistically significant differences compared with the control, p<0.05. # Statistically significant difference compared with the H2O2—treated group.
Hi Ben. Have a groin problem which I have had for years and it just won’t go away it’s not a hernia or osteitis pubis I had an MRI and the specialist said they wouldn’t operate. I can still play sport but I’m just less agile and slower than normal and it takes a few days for the groin pain to go away after sport. Would tb500 help to heal it or would bpc157 or something else be better? Thanks :)
Dr Sohère Roked is a GP in the UK with a specialist interest in integrative medicine. She prescribes 5-HTP to patients with anxiety and depression, alongside vitamins and other natural supplements, and sees no problem with it being used for mild conditions. "With the patients I see, generally I've seen good results with it. Antidepressants do work for some people, so I'm not against them completely, but others don't want to go down that path straight away. This gives them another option."

The relationship between oxytocin and human sexual response is unclear. At least two non-controlled studies have found increases in plasma oxytocin at orgasm in both men and women.[5][6] The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.[5] Murphy et al. (1987), studying men, found that oxytocin levels were raised throughout sexual arousal and there was no acute increase at orgasm. [7] A more recent study of men found an increase in plasma oxytocin immediantly after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted that these changes "may simply reflect contractile properties on reproductive tissue."[8]
Uterine contraction important for cervical dilation before birth and causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful uterine contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition is normal.[4]
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For decades, 5-HTP has been recognized as important to appetite regulation. Higher levels of serotonin are linked to diminished appetite. Keeping serotonin levels from dipping can help keep appetite in check, and may help reduce cravings for carbohydrates. As a serotonin booster, 5-HTP may help to suppress appetite. Research indicates that 5-HTP may be effective in helping people who are overweight or obese lose weight.